Scholars@Duke
Soman Ninan Abraham

Soman Ninan Abraham

Grace Kerby Distinguished Professor of Pathology
Pathology
soman.abraham@duke.edu
Duke Box 3172, Durham, NC 27710
257 Jones Bldg, Durham, NC 27710

Selected Publications

Reply.

Journal Article J Allergy Clin Immunol · October 2024 Full text Link to item Cite

Mastoparan-7 adjuvanted COBRA H1 and H3 hemagglutinin influenza vaccines.

Journal Article Sci Rep · June 14, 2024 Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and elderly. Most adjuvants are formulated with injectable vaccines. However, an intranasal ro ... Full text Link to item Cite

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

Journal Article Vet Dermatol · June 2024 BACKGROUND: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the n ... Full text Link to item Cite

Mast cell-sensory neuron crosstalk in allergic diseases.

Journal Article J Allergy Clin Immunol · April 2024 Mast cells (MCs) are tissue-resident immune cells, well-positioned at the host-environment interface for detecting external antigens and playing a critical role in mobilizing innate and adaptive immune responses. Sensory neurons are afferent neurons innerv ... Full text Link to item Cite

Anaphylactic degranulation by mast cells requires the mobilization of inflammasome components.

Journal Article Nat Immunol · April 2024 The inflammasome components NLRP3 and ASC are cytosolic proteins, which upon sensing endotoxins or danger cues, form multimeric complexes to process interleukin (IL)-1β for secretion. Here we found that antigen (Ag)-triggered degranulation of IgE-sensitize ... Full text Link to item Cite

Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.

Journal Article Sci Immunol · March 2024 Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the b ... Full text Link to item Cite

Stabilization of activated mast cells by ORAI1 inhibitor suppresses peanut-induced anaphylaxis and acute diarrhea.

Journal Article Pharmacol Res · October 2023 Mast cell (MC) activation triggered by immunoglobulin E (IgE)-antigen crosslinking involves intracellular Ca2+ influx through the ORAI1 channel, which precedes granule exteriorization and de novo synthesis of mediators. Pharmacologically suppressing MCs vi ... Full text Link to item Cite

α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification.

Journal Article PLoS Pathog · May 2023 There is a growing consensus that a significant proportion of recurrent urinary tract infections are linked to the persistence of uropathogens within the urinary tract and their re-emergence upon the conclusion of antibiotic treatment. Studies in mice and ... Full text Link to item Cite

Mast Cells as a Target-A Comprehensive Review of Recent Therapeutic Approaches.

Journal Article Cells · April 19, 2023 Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and ... Full text Link to item Cite

A mast cell-thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis.

Journal Article Sci Immunol · March 17, 2023 IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an e ... Full text Link to item Cite

Delivery of small molecule mast cell activators for West Nile Virus vaccination using acetalated dextran microparticles.

Journal Article Int J Pharm · March 5, 2023 Recently, there has been increasing interest in the activation of mast cells to promote vaccine efficacy. Several mast cell activating (MCA) compounds have been reported such as M7 and Compound 48/80 (C48/80). While these MCAs have been proven to be effica ... Full text Link to item Cite

Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG.

Journal Article Front Immunol · 2023 Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging as a target for a new class of mucosal vaccine adjuvants. Here, we developed and c ... Full text Link to item Cite

Mast cell regranulation requires a metabolic switch involving mTORC1 and a glucose-6-phosphate transporter.

Journal Article Cell Rep · September 27, 2022 Mast cells (MCs) are granulated cells implicated in inflammatory disorders because of their capacity to degranulate, releasing prestored proinflammatory mediators. As MCs have the unique capacity to reform granules following degranulation in vitro, their p ... Full text Link to item Cite

Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response.

Journal Article Proc Natl Acad Sci U S A · August 16, 2022 Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to anti ... Full text Link to item Cite

Structure, function and pharmacology of human itch GPCRs.

Journal Article Nature · December 2021 The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently1. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated ... Full text Link to item Cite

Local induction of bladder Th1 responses to combat urinary tract infections.

Journal Article Proc Natl Acad Sci U S A · March 9, 2021 Given the high frequency of urinary tract infections (UTIs) and their recurrence, there is keen interest in developing effective UTI vaccines. Currently, most vaccine studies, including those in humans, involve parenteral vaccination aimed at evoking and s ... Full text Link to item Cite

The Roles of T cells in Bladder Pathologies.

Journal Article Trends Immunol · March 2021 T lymphocytes play important roles in the skin and mucosal surfaces such as the gut and lung. Until recently the contributions of T cells to mammalian bladder immunity were largely unknown. With newer techniques, including single-cell RNA sequencing and re ... Full text Link to item Cite

Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.

Journal Article Front Immunol · 2021 Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. Howe ... Full text Link to item Cite

Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.

Journal Article Viruses · December 2, 2020 Dengue virus (DENV), an arbovirus, strongly activates mast cells (MCs), which are key immune cells for pathogen immune surveillance. In animal models, MCs promote clearance of local peripheral DENV infections but, conversely, also promote pathological vasc ... Full text Link to item Cite

Introducing a novel experimental model of bladder transplantation in mice.

Journal Article Am J Transplant · December 2020 Bladder dysfunction is a common clinical problem attributed to various conditions such as posterior urethral valves, neurogenic bladder, ureteral ectopy, or bladder exstrophy. Currently, the main therapeutic option for these dysfunctions is neobladder reco ... Full text Link to item Cite

A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections.

Journal Article Nat Immunol · June 2020 Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune ... Full text Link to item Cite

A humanized mouse model to study mast cells mediated cutaneous adverse drug reactions.

Journal Article J Leukoc Biol · May 2020 Recently a G-protein-coupled receptor, MAS Related GPR Family Member X2 (MRGPRX2), was identified as a specific receptor on human mast cells responsible for IgE independent adverse drug reactions (ADR). Although a murine homologue, Mrgprb2, has been identi ... Full text Link to item Cite

Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.

Journal Article Sci Adv · March 2020 Platelet responses have been associated with end-organ injury and mortality following complex insults such as cardiac surgery, but how platelets contribute to these pathologies remains unclear. Our studies originated from the observation of microvascular p ... Full text Link to item Cite

Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

Journal Article NPJ Vaccines · February 5, 2020 Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, m ... Full text Link to item Cite

Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

Journal Article NPJ Vaccines · 2020 Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, m ... Full text Open Access Link to item Cite

Innate Immunity based Mucosal Modulators and Adjuvants

Chapter · 2020 The development of mucosally administered vaccines remains a goal of many researchers who desire to develop a needle-free method of immunization that can induce antigen-specific immune responses in both systemic and mucosal tissues. The coadministration of ... Full text Link to item Cite

Innate Immunity-Based Mucosal Modulators and Adjuvants

Chapter · September 15, 2019 The development of mucosally administered vaccines remains a goal of many researchers who desire to develop a needle-free method of immunization that can induce antigen-specific immune responses in both systemic and mucosal tissues. The coadministration of ... Link to item Cite

Mast Cells For the Control of Mucosal Immunity

Chapter · September 15, 2019 Mast cells (MCs) are gaining recognition as key initiators and coordinators of host inflammatory and immune responses to various microbial pathogens. Their presence in mucosal tissues and skin make them one of the first immune cells to make contact with in ... Link to item Cite

Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen.

Journal Article J Virol · July 15, 2019 The benefits of mucosal vaccines over injected vaccines are difficult to ascertain, since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if muc ... Full text Link to item Cite

Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.

Journal Article SLAS Discov · July 2019 Mast cells (MCs) are known to regulate innate and adaptive immunity. MC activators have recently been described as safe and effective vaccine adjuvants. Many currently known MC activators are inadequate for in vivo applications, however, and research on id ... Full text Link to item Cite

MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection.

Journal Article Sci Adv · January 2019 Featured Publication Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, ... Full text Open Access Link to item Cite

Autoimmune Theories of Chronic Spontaneous Urticaria.

Journal Article Front Immunol · 2019 Urticaria (hives) is a highly prevalent skin disorder that can occur with or without associated angioedema. Chronic spontaneous urticaria (CSU) is a condition which persists for more than 6 weeks in duration and occurs in the absence of an identifiable pro ... Full text Link to item Cite

Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles.

Journal Article Science · November 9, 2018 Featured Publication Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive ... Full text Link to item Cite

Necroptosis of infiltrated macrophages drives Yersinia pestis dispersal within buboes.

Journal Article JCI Insight · September 20, 2018 Featured Publication When draining lymph nodes become infected by Yersinia pestis (Y. pestis), a massive influx of phagocytic cells occurs, resulting in distended and necrotic structures known as buboes. The bubonic stage of the Y. pestis life cycle precedes septicemia, which ... Full text Link to item Cite

Mast cell activators as novel immune regulators.

Journal Article Curr Opin Pharmacol · August 2018 Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node compositi ... Full text Link to item Cite

Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells.

Journal Article Sci Adv · July 2018 How previous immunity influences immune memory recall and protection against related flaviviruses is largely unknown, yet encounter with multiple flaviviruses in a lifetime is increasingly likely. Using sequential challenges with dengue virus (DENV), yello ... Full text Link to item Cite

Reprograming immunity to food allergens.

Journal Article J Allergy Clin Immunol · May 2018 Featured Publication A novel immune-modulatory therapy utilizing targeted delivery of cytokines to draining lymph nodes effectively reprograms Th2 allergic responses towards a Th1 and tolerogenic profile, resulting in protection from peanut antigen-induced anaphylaxis. ... Full text Link to item Cite

In Vitro and In Vivo IgE-/Antigen-Mediated Mast Cell Activation.

Journal Article Methods Mol Biol · 2018 Mast cells (MCs) are major effectors of IgE-mediated allergic reactions because of their unique peripheral location and their powerful capacity to release prestored and de novo-synthesized inflammatory mediators into the circulation upon activation. In vie ... Full text Link to item Cite

Collaboration between Distinct Rab Small GTPase Trafficking Circuits Mediates Bacterial Clearance from the Bladder Epithelium.

Journal Article Cell Host Microbe · September 13, 2017 Featured Publication Rab small GTPases control membrane trafficking through effectors that recruit downstream mediators such as motor proteins. Subcellular trafficking typically involves multiple Rabs, with each specific step mediated by a distinct Rab protein. We describe a c ... Full text Link to item Cite

Targeting Deficiencies in the TLR5 Mediated Vaginal Response to Treat Female Recurrent Urinary Tract Infection.

Journal Article Sci Rep · September 8, 2017 The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, pa ... Full text Link to item Cite

IL-27 Facilitates Skin Wound Healing through Induction of Epidermal Proliferation and Host Defense.

Conference J Invest Dermatol · May 2017 Skin wound repair requires a coordinated program of epithelial cell proliferation and differentiation as well as resistance to invading microbes. However, the factors that trigger epithelial cell proliferation in this inflammatory process are incompletely ... Full text Open Access Link to item Cite

The multiple antibacterial activities of the bladder epithelium.

Journal Article Ann Transl Med · January 2017 The urinary tract is subject to frequent challenges from the gut microflora. Indeed, up to 40% of women will experience at least one urinary tract infection (UTI) during their lifetime. Uropathogenic Escherichia coli (UPEC) contribute to an overwhelming ma ... Full text Link to item Cite

Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules.

Journal Article Immunity · December 20, 2016 Featured Publication Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cysti ... Full text Link to item Cite

Innate Immune Responses to Bladder Infection.

Journal Article Microbiol Spectr · December 2016 Urinary tract infections are one of the most frequent bacterial infections of mankind. In spite of this frequency, the study of the immune system in the urinary tract has not attracted much attention. This could, in part, be attributable to the widespread ... Full text Link to item Cite

Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.

Journal Article J Clin Invest · November 1, 2016 Featured Publication Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have impl ... Full text Link to item Cite

How mast cells make decisions.

Journal Article J Clin Invest · October 3, 2016 Featured Publication Mast cells (MCs) are present in various tissues and are responsible for initiating many of the early inflammatory responses to extrinsic challenges. Recent studies have demonstrated that MCs can tailor their responses, depending on the stimulus encountered ... Full text Link to item Cite

Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of Intracellular Bacteria by Exocyst Complex.

Journal Article Immunity · July 19, 2016 Featured Publication Although the intracellular trafficking system is integral to most physiologic activities, its role in mediating immune responses to infection has remained elusive. Here, we report that infected bladder epithelial cells (BECs) mobilized the exocyst complex, ... Full text Link to item Cite

Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation.

Journal Article Mucosal Immunol · May 2016 Invariant natural killer T (iNKT) cells produce cytokines interleukin-4 (IL-4) and IL-13 during type-2 inflammatory responses. However, the nature in which iNKT cells acquire type-2 cytokine competency and the precise contribution of iNKT cell-derived IL-4 ... Full text Link to item Cite

Innate immune responses to bladder infection

Chapter · April 19, 2016 The urinary tract (UT) consists of the kidneys, ureters, bladder, and urethra, all of which with the exception of the lower urethra are presumed to be sterile. Because of its close proximity to the gut, the lower UT is constantly exposed to a barrage of gu ... Full text Cite

Why Serological Responses during Cystitis are Limited.

Journal Article Pathogens · February 14, 2016 The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host's memory immune response. It has been known for many decades that, whereas kidney i ... Full text Open Access Link to item Cite

The nature of immune responses to urinary tract infections.

Journal Article Nat Rev Immunol · October 2015 Featured Publication The urinary tract is constantly exposed to microorganisms that inhabit the gastrointestinal tract, but generally the urinary tract resists infection by gut microorganisms. This resistance to infection is mainly ascribed to the versatility of the innate imm ... Full text Link to item Cite

A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion.

Journal Article Cell · June 4, 2015 Featured Publication Vertebrate cells have evolved elaborate cell-autonomous defense programs to monitor subcellular compartments for infection and to evoke counter-responses. These programs are activated by pathogen-associated pattern molecules and by various strategies intra ... Full text Link to item Cite

Mast cell mediator responses and their suppression by pathogenic and commensal microorganisms.

Journal Article Mol Immunol · January 2015 Mast cells (MCs) are selectively found at the host environment interface and are capable of secreting a wide array of pharmacologically active mediators, many of which are prepackaged in granules. Over the past two decades, it has become clear that these c ... Full text Link to item Cite

Complete genome sequence of uropathogenic Escherichia coli strain CI5

Journal Article Genome Announcements · January 1, 2015 Escherichia coli represents the primary etiological agent responsible for urinary tract infections, one of the most common infections in humans. We report here the complete genome sequence of uropathogenic Escherichia coli strain CI5, a clinical pyelonephr ... Full text Cite

S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.

Journal Article Immunity · September 18, 2014 Featured Publication Pathologically swollen lymph nodes (LNs), or buboes, characterize Yersinia pestis infection, yet how they form and function is unknown. We report that colonization of the draining LN (dLN) occurred due to trafficking of infected dendritic cells and monocyt ... Full text Link to item Cite

Cromolyn ameliorates acute and chronic injury in a rat lung transplant model.

Journal Article J Heart Lung Transplant · July 2014 BACKGROUND: Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown. METHODS: In this study, we evaluated the role of mast cells in pulmonary allograft ... Full text Link to item Cite

Kidney α-intercalated cells and lipocalin 2: defending the urinary tract.

Journal Article J Clin Invest · July 2014 A growing body of evidence indicates that the kidneys contribute substantially to immune defense against pathogens in the urinary tract. In this issue, Paragas et al. report that α-intercalated cells (A-ICs) within the nephron collecting duct sense infecti ... Full text Link to item Cite

Peeing pentraxins.

Journal Article Immunity · April 17, 2014 Featured Publication Antimicrobial agents secreted into urine potentially play a powerful role in the defense of the urinary tract. In this issue of Immunity, Jaillon et al. (2014) describe a role for pentraxin 3 molecules in complementing the host's cellular innate immune res ... Full text Link to item Cite

Adhesion and Colonization

Chapter · January 1, 2014 The binding of bacterial adhesins to host receptors is a dynamic process occurring in several steps, which involve complex bacteria-host cell interaction. Initial weak physical interactions lead to more specific adhesion mechanisms that may be shared by se ... Full text Cite

Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing protein tyrosine phosphatase, SptP.

Journal Article Immunity · December 12, 2013 Featured Publication The virulence of Salmonella is linked to its invasive capacity and suppression of adaptive immunity. This does not explain, however, the rapid dissemination of the pathogen after it breaches the gut. In our study, S. Typhimurium suppressed degranulation of ... Full text Link to item Cite

Bacterial adhesion

Chapter · November 1, 2013 Although bacteria adhere to many different types of surfaces present in their habitat, this review focuses on bacterial adhesion to animal cells and tissues as a first step in the ability of pathogens to colonize and subsequently cause tissue damage. Accor ... Full text Cite

A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses.

Journal Article Peptides · October 2013 Broad-spectrum antiviral drugs are urgently needed to treat individuals infected with new and re-emerging viruses, or with viruses that have developed resistance to antiviral therapies. Mammalian natural host defense peptides (mNHP) are short, usually cati ... Full text Link to item Cite

Intestinal mast cells mediate gut injury and systemic inflammation in a rat model of deep hypothermic circulatory arrest.

Journal Article Crit Care Med · September 2013 OBJECTIVE: Cardiac surgery, especially when employing cardiopulmonary bypass and deep hypothermic circulatory arrest, is associated with systemic inflammatory responses that significantly affect morbidity and mortality. Intestinal perfusion abnormalities h ... Full text Link to item Cite

Interplay between vesicoureteric reflux and kidney infection in the development of reflux nephropathy in mice.

Journal Article Dis Model Mech · July 2013 Featured Publication Vesicoureteric reflux (VUR) is a common congenital defect of the urinary tract that is usually discovered after a child develops a urinary tract infection. It is associated with reflux nephropathy, a renal lesion characterized by the presence of chronic tu ... Full text Link to item Cite

Barriers to preclinical investigations of anti-dengue immunity and dengue pathogenesis.

Journal Article Nat Rev Microbiol · June 2013 Featured Publication Dengue virus (DENV) is a human pathogen that causes severe and potentially fatal disease in millions of individuals each year. Immune-mediated pathology is thought to underlie many of the complications of DENV infection in humans, but the notable limitatio ... Full text Link to item Cite

Innate immunity and its regulation by mast cells.

Journal Article J Immunol · May 1, 2013 Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, constitute a major sensory arm of the innate immune system. In this review we discuss the evidence supporting the dual role of MCs, both as sentinels for invading pathog ... Full text Link to item Cite

Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.

Journal Article Elife · April 30, 2013 Featured Publication Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unkn ... Full text Open Access Link to item Cite

A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen.

Journal Article Vaccine · March 1, 2013 Development of nasal immunization for human use is hindered by the lack of acceptable adjuvants. Although CT is an effective adjuvant, its toxicity will likely prevent its use in nasal vaccines. This study compared non-toxin adjuvants to CT for their abili ... Full text Link to item Cite

Mast cell interleukin-10 drives localized tolerance in chronic bladder infection.

Journal Article Immunity · February 21, 2013 Featured Publication The lower urinary tract's virtually inevitable exposure to external microbial pathogens warrants efficient tissue-specialized defenses to maintain sterility. The observation that the bladder can become chronically infected in combination with clinical obse ... Full text Link to item Cite

A Mast Cell Degranulation Screening Assay for the Identification of Novel Mast Cell Activating Agents.

Journal Article Medchemcomm · January 1, 2013 The development and use of vaccines and their ability to prevent infection/disease is a shining example of the benefit of biomedical research. Modern vaccines often utilize subunit immunogens that exhibit minimal immunogenicity and require the use of adjuv ... Full text Link to item Cite

Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

Journal Article eLife · 2013 Featured Publication Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unkn ... Full text Cite

Mast cell TNF receptors regulate responses to Mycoplasma pneumoniae in surfactant protein A (SP-A)-/- mice.

Journal Article J Allergy Clin Immunol · July 2012 BACKGROUND: Mycoplasma pneumoniae (Mp) frequently colonizes the airways of patients with chronic asthma and likely contributes to asthma exacerbations. We previously reported that mice lacking surfactant protein A (SP-A) have increased airway hyperresponsi ... Full text Link to item Cite

Convergent Evolution of Calcineurin Pathway Roles in Thermotolerance and Virulence in Candida glabrata.

Journal Article G3 (Bethesda) · June 2012 Candida glabrata is an emerging human fungal pathogen that is frequently drug tolerant, resulting in difficulties in treatment and a higher mortality in immunocompromised patients. The calcium-activated protein phosphatase calcineurin plays critical roles ... Full text Link to item Cite

Plasticity in mast cell responses during bacterial infections.

Journal Article Curr Opin Microbiol · February 2012 Mast cells (MCs) have been implicated in orchestrating the host's early innate immune and adaptive immune responses in several models of acute bacterial infections. Most of this activity results in early clearance of the bacteria and timely resolution of i ... Full text Link to item Cite

Increased Nitric Oxide Production Prevents Airway Hyperresponsiveness in Caveolin-1 Deficient Mice Following Endotoxin Exposure.

Journal Article J Allergy Ther · January 25, 2012 BACKGROUND: Caveolin-1, the hallmark protein of caveolae, is highly expressed within the lung in the epithelium, endothelium, and in immune cells. In addition to its classical roles in cholesterol metabolism and endocytosis, caveolin-1 has also been shown ... Full text Link to item Cite

Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes.

Journal Article Nat Mater · January 22, 2012 Featured Publication Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic parti ... Full text Link to item Cite

Stable dry powder formulation for nasal delivery of anthrax vaccine.

Journal Article J Pharm Sci · January 2012 There is a current biodefense interest in protection against anthrax. Here, we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by recombinant protective antigen (rPA) delivered intranasally with a ... Full text Link to item Cite

Mast cell modulation of the vascular and lymphatic endothelium.

Journal Article Blood · November 17, 2011 Featured Publication Mast cells (MCs) promote a wide range of localized and systemic inflammatory responses. Their involvement in immediate as well as chronic inflammatory reactions at both local and distal sites points to an extraordinarily powerful immunoregulatory capacity ... Full text Link to item Cite

c-Kit is essential for alveolar maintenance and protection from emphysema-like disease in mice.

Journal Article Am J Respir Crit Care Med · June 15, 2011 RATIONALE: Previously, we demonstrated a candidate region for susceptibility to airspace enlargement on mouse chromosome 5. However, the specific candidate genes within this region accounting for emphysema-like changes remain unrecognized. c-Kit is a recep ... Full text Link to item Cite

Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance.

Journal Article Proc Natl Acad Sci U S A · May 31, 2011 Featured Publication A wealth of evidence supports the essential contributions of mast cells (MCs) to immune defense against bacteria and parasites; however, the role of MCs in viral infections has not been defined. We now report that rodent, monkey, and human MCs are able to ... Full text Link to item Cite

Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.

Journal Article J Clin Invest · March 2011 Featured Publication Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic asthma with an increase in ambient inhalable partic ... Full text Link to item Cite

Mucosal targeting of a BoNT/A subunit vaccine adjuvanted with a mast cell activator enhances induction of BoNT/A neutralizing antibodies in rabbits.

Journal Article PLoS One · January 27, 2011 BACKGROUND: We previously reported that the immunogenicity of Hcβtre, a botulinum neurotoxin A (BoNT/A) immunogen, was enhanced by fusion to an epithelial cell binding domain, Ad2F, when nasally delivered to mice with cholera toxin (CT). This study was per ... Full text Link to item Cite

The mast cell in innate and adaptive immunity.

Journal Article Adv Exp Med Biol · 2011 Mast cells (MCs) were once considered only as effector cells in pathogenic IgE- and IgG-mediated responses such as allergy. However, developments over the last 15 years have suggested that MCs have evolved in vertebrates as beneficial effector cells that a ... Full text Link to item Cite

C-KIT Is Necessary For Protection From Emphysema-Like Disease In Mice

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2011 Link to item Cite

Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.

Journal Article PLoS One · August 17, 2010 BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are ... Full text Open Access Link to item Cite

Mast cell-orchestrated immunity to pathogens.

Journal Article Nat Rev Immunol · June 2010 Featured Publication Although mast cells were discovered more than a century ago, their functions beyond their role in allergic responses remained elusive until recently. However, there is a growing appreciation that an important physiological function of these cells is the re ... Full text Link to item Cite

New roles for mast cells in pathogen defense and allergic disease.

Journal Article Discov Med · February 2010 Mast cells (MC) are specialized exocytic cells that lie beneath the external surfaces of the body. For many decades, MCs were thought to primarily function as effector cells for IgE mediated allergic diseases. However, recent evidence indicates that MCs al ... Link to item Cite

An In Vitro Model of Mast Cell Desensitization

Conference Journal of Allergy and Clinical Immunology · February 2010 Full text Cite

Cell biology and physiology of the uroepithelium.

Journal Article Am J Physiol Renal Physiol · December 2009 The uroepithelium sits at the interface between the urinary space and underlying tissues, where it forms a high-resistance barrier to ion, solute, and water flux, as well as pathogens. However, the uroepithelium is not simply a passive barrier; it can modu ... Full text Link to item Cite

New roles for mast cells in modulating allergic reactions and immunity against pathogens.

Journal Article Curr Opin Immunol · December 2009 Featured Publication Mast cells (MCs) have primarily been associated with mediating the pathological secondary responses to allergens in sensitized hosts. In view of the recent evidence for a MC role in modulating primary immune responses to pathogens, the likelihood for a rol ... Full text Link to item Cite

Mast cell activator as a mucosal adjuvant in intranasal pertussis vaccine

Conference CLINICAL AND EXPERIMENTAL ALLERGY · December 1, 2009 Link to item Cite

Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines.

Journal Article Nat Med · November 2009 Featured Publication We report that infection of draining lymph nodes (DLNs) by Salmonella typhimurium results in the specific downregulation of the homeostatic chemokines CCL21 and CXCL13, which are essential for normal DLN organization and function. Our data reveal that the ... Full text Link to item Cite

The expanding roles of caveolin proteins in microbial pathogenesis.

Journal Article Commun Integr Biol · November 2009 Caveolin proteins have been implicated in a wide range of cellular functions including lipid raft mediated endocytosis and regulation of cell signaling cascades. Recent discoveries have shown that these proteins are involved not only in regulating these ho ... Full text Link to item Cite

Mast cell-derived particles deliver peripheral signals to remote lymph nodes.

Journal Article J Exp Med · October 26, 2009 Featured Publication During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that ... Full text Link to item Cite

Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues.

Journal Article Cell Host Microbe · October 22, 2009 Featured Publication Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the seru ... Full text Link to item Cite

TLR4-mediated expulsion of bacteria from infected bladder epithelial cells.

Journal Article Proc Natl Acad Sci U S A · September 1, 2009 Featured Publication Uropathogenic Escherichia coli invade bladder epithelial cells (BECs) by direct entry into specialized cAMP regulated exocytic compartments. Remarkably, a significant number of these intracellular bacteria are subsequently expelled in a nonlytic and piecem ... Full text Link to item Cite

Involvement of dynamin-2 in formation of discoid vesicles in urinary bladder umbrella cells.

Journal Article Cell Tissue Res · July 2009 Umbrella cells (UCs) of the epithelium of the urinary bladder have the capacity to control bladder volume by regulating exocytosis/endocytosis of their intracellular discoid vesicles (DVs). Dynamin (Dyn) is a GTPase that promotes endocytic processes throug ... Full text Link to item Cite

The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigen.

Journal Article Vaccine · June 2, 2009 We evaluated the safety and efficacy of the mast cell activator compound 48/80 (C48/80) when used as an adjuvant delivered intradermally (ID) with recombinant anthrax protective antigen (rPA) in comparison with two well-known adjuvants. Mice were vaccinate ... Full text Link to item Cite

Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa.

Journal Article J Biol Chem · April 10, 2009 Featured Publication Pseudomonas aeruginosa has the capacity to invade lung epithelial cells by co-opting the intrinsic endocytic properties of lipid rafts, which are rich in cholesterol, sphingolipids, and proteins, such as caveolin-1 and -2. We compared intratracheal Pseudom ... Full text Link to item Cite

Use of a Mast Cell Activator as a Mucosal Adjuvant for Pertussis Vaccines

Journal Article Journal of Allergy and Clinical Immunology · February 2009 Full text Cite

AHR Is Attenuated in Caveolin-1 Deficient Mice

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2009 Link to item Cite

Mast Cells Are Required for the Development of Allograft Rejection in a Murine Model of Obliterative Bronchiolitis

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2009 Link to item Cite

Innate and adaptive immune responses in the urinary tract.

Journal Article Eur J Clin Invest · October 2008 As new and intriguing details of how uropathogens initiate infections and persist within the urinary tract have emerged, so has important information regarding how the immune system functions within the urinary tract. Recent studies have revealed the exist ... Full text Link to item Cite

Mast cell activators: a new class of highly effective vaccine adjuvants.

Journal Article Nat Med · May 2008 Featured Publication Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, ... Full text Link to item Cite

TLR-mediated immune responses in the urinary tract.

Journal Article Curr Opin Microbiol · February 2008 Featured Publication The urinary tract is one of the most intractable mucosal surfaces for pathogens to colonize. In addition to the natural barriers at this site, potential pathogens have to contend with the vigorous local innate immune system. Several Toll-like receptors (TL ... Full text Link to item Cite

TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder.

Journal Article Cell Host Microbe · June 14, 2007 Featured Publication The remarkable resistance of the urinary tract to infection has been attributed to its physical properties and the innate immune responses triggered by pattern recognition receptors lining the tract. We report a distinct TLR4 mediated mechanism in bladder ... Full text Link to item Cite

Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells.

Journal Article Nat Med · May 2007 Featured Publication The superficial bladder epithelium is a powerful barrier to urine and also serves as a regulator of bladder volume, which is achieved by apical exocytosis of specialized fusiform vesicles during distension of the bladder. We report that type 1 fimbriated u ... Full text Link to item Cite

Mast cells enable heightened humoral immunity during infection

Journal Article JOURNAL OF IMMUNOLOGY · April 1, 2007 Link to item Cite

A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.

Journal Article PLoS Pathog · April 2007 Featured Publication The vigorous cytokine response of immune cells to Gram-negative bacteria is primarily mediated by a recognition molecule, Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide (LPS) and initiates a series of intracellular NF-kappaB-associated si ... Full text Link to item Cite

Attenuated virulence of a Francisella mutant lacking the lipid A 4'-phosphatase.

Journal Article Proc Natl Acad Sci U S A · March 6, 2007 Francisella tularensis causes tularemia, a highly contagious disease of animals and humans, but the virulence features of F. tularensis are poorly defined. F. tularensis and the related mouse pathogen Francisella novicida synthesize unusual lipid A molecul ... Full text Link to item Cite

A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells.

Journal Article PLoS pathogens · 2007 Featured Publication The vigorous cytokine response of immune cells to Gram-negative bacteria is primarily mediated by a recognition molecule, Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide (LPS) and initiates a series of intracellular NF-kappaB-associated si ... Full text Cite

Harboring of particulate allergens within secretory compartments by mast cells following IgE/FcepsilonRI-lipid raft-mediated phagocytosis.

Journal Article J Immunol · November 1, 2006 Although much is known regarding the exocytic responses of mast cells following allergen/IgE-mediated activation, little is currently known of the fate of the activating allergens, many of which are particles. We have found that IgE-bound particulate aller ... Full text Link to item Cite

Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production.

Journal Article Eukaryot Cell · June 2006 The fungal secondary metabolite gliotoxin produced by Aspergillus fumigatus has been hypothesized to be important in the development of invasive aspergillosis. In this study, we addressed this hypothesis by disrupting a nonribosomal peptide synthetase (NRP ... Full text Link to item Cite

In vivo models for studying mast cell-dependent responses to bacterial infection.

Journal Article Methods Mol Biol · 2006 Mast cells are a critical component of host defense against bacterial infections. Activation of these cells during infection induces both innate and adaptive aspects of protective immunity needed for the elimination of the bacteria and survival of the host ... Full text Link to item Cite

The role of lipid rafts in the pathogenesis of bacterial infections.

Journal Article Biochim Biophys Acta · December 30, 2005 Numerous pathogens have evolved mechanisms of co-opting normal host endocytic machinery as a means of invading host cells. While numerous pathogens have been known to enter cells via traditional clathrin-coated pit endocytosis, a growing number of viral an ... Full text Link to item Cite

Chapter 4 Lipid Raft-Mediated Entry of Bacteria into Host Cells

Journal Article Advances in Molecular and Cell Biology · December 1, 2005 Many bacterial pathogens are known to enter into host cells, either as a means of avoiding the host immune system or as an integral part of their replicative cycle. One major hurdle intracellular pathogens must overcome is degradation in the classical endo ... Full text Cite

Adhesion of bacteria to mucosal surfaces

Journal Article · December 1, 2005 This chapter discusses about bacterial adhesions and their mucosal cell receptors. It also discusses selected postadhesion events and describes how they influence mucosal colonization. The specific binding interaction between the bacterial adhesions and ho ... Full text Cite

The distinct binding specificities exhibited by enterobacterial type 1 fimbriae are determined by their fimbrial shafts.

Journal Article J Biol Chem · November 11, 2005 Featured Publication Type 1 fimbriae of enterobacteria are heteropolymeric organelles of adhesion composed of FimH, a mannose-binding lectin, and a shaft composed primarily of FimA. We compared the binding activities of recombinant clones expressing type 1 fimbriae from Escher ... Full text Link to item Cite

Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation.

Journal Article Am J Physiol Lung Cell Mol Physiol · November 2005 Mast cells play a key role in allergy and asthma. They reside at the host-environment interface and are among the first cells to make contact with inhaled microorganisms and particulate antigens. Pulmonary surfactant proteins A and D (SP-A and SP-D) functi ... Full text Link to item Cite

Bacterial penetration of the mucosal barrier by targeting lipid rafts.

Journal Article J Investig Med · September 2005 Several traditionally extracellular pathogens not known to possess invasive capacity have been shown to invade various mucosal epithelial cells. The mucosal epithelium performs an important barrier function and is not typically amenable to bacterial invasi ... Full text Link to item Cite

Pseudomonas invasion of type I pneumocytes is dependent on the expression and phosphorylation of caveolin-2.

Journal Article J Biol Chem · February 11, 2005 Pseudomonas aeruginosa is a major cause of pneumonia in patients with cystic fibrosis and other immuncompromising conditions. Here we showed that P. aeruginosa invades type I pneumocytes via a lipid raft-mediated mechanism. P. aeruginosa invasion of rat pr ... Full text Link to item Cite

Bacterial penetration of bladder epithelium through lipid rafts.

Journal Article J Biol Chem · April 30, 2004 Type 1 fimbriated Escherichia coli represents the most common human uropathogen, owing much of its virulence to invasion of the uroepithelium, which is highly impermeable due to the preponderance of uroplakins and highly ordered lipid components. We sought ... Full text Link to item Cite

Contribution of mast cells to bacterial clearance and their proliferation during experimental cystitis induced by type 1 fimbriated E. coli.

Journal Article Immunol Lett · February 15, 2004 Bacterial infections of the urinary bladder are very common, and the role of mast cells in these infections is invariably thought of as a detrimental one. However, recent studies have shown that mast cells play a key role in host defense against various en ... Full text Link to item Cite

Differential mast cell response to different bacteria

Journal Article Journal of Bacteriology and Virology · January 1, 2004 Mast cells (MCs) are highly specialized for the synthesis and secretion of pharmacologically active products. Although implicated in various inflammatory diseases such as asthma, allergy, multiple sclerosis, and Crohn's disease, MCs have also an important ... Cite

Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection.

Journal Article Nat Immunol · December 2003 Featured Publication Palpable swelling of regional lymph nodes is a common sequela of microbial infections but the mechanism responsible for the sequestration and subsequent coordination of lymphocyte responses within these dynamic structures remains poorly understood. Here we ... Full text Link to item Cite

Mast cell activation by Mycobacterium tuberculosis: mediator release and role of CD48.

Journal Article J Immunol · June 1, 2003 Mast cells (MC) are abundant in the lung and other peripheral tissue, where they participate in inflammatory processes against bacterial infections. Like other effector cells of the innate immune system, MC interact directly with a wide variety of infectio ... Full text Link to item Cite

Microbial entry through caveolae: variations on a theme.

Journal Article Cell Microbiol · December 2002 Caveolae and lipid rafts are increasingly being recognized as a significant portal of entry into host cells for a wide variety of pathogenic microorganisms. Entry through this mechanism appears to afford the microbes protection from degradation in lysosome ... Full text Link to item Cite

The role of mast cells in host defense and their subversion by bacterial pathogens.

Journal Article Trends Immunol · March 2002 Mast cells (MCs) play a prominent role in the early immune response to invading pathogenic bacteria. This newly discovered role for MCs involves the release of chemoattractants that recruit neutrophils and the direct phagocytosis and killing of opsonized b ... Full text Link to item Cite

Cell biology. Caveolae--not just craters in the cellular landscape.

Journal Article Science · August 24, 2001 Featured Publication Full text Link to item Cite

Caveolae as portals of entry for microbes.

Journal Article Microbes Infect · July 2001 Many pathogens, including many traditionally extracellular microbes, now appear capable of entry into host cells with limited loss of viability. A portal of entry shared by some bacteria, bacterial toxins, viruses and parasites are caveolae (or lipid rafts ... Full text Link to item Cite

Studies of the multifaceted mast cell response to bacteria.

Journal Article Curr Opin Microbiol · June 2001 Featured Publication The concept of mast cells as playing a critical and multifaceted role in immune defense against pathogens is new, and effective ways to study and validate this notion are required. Recently, a number of approaches have been described that can be used to st ... Full text Link to item Cite

Glycosylphosphatidylinositol-anchored receptor-mediated bacterial endocytosis.

Journal Article FEMS Microbiol Lett · April 13, 2001 An increasing number of pathogens or their toxins appear to utilize glycosylphosphatidylinositol(GPI)-anchored receptors to trigger entry into immune and other host cells. Since these receptors have no transmembrane and intracellular moieties, how endocyto ... Full text Link to item Cite

Interaction of Bordetella pertussis with mast cells, modulation of cytokine secretion by pertussis toxin.

Journal Article Cell Microbiol · March 2001 Together with macrophages and dendritic cells, mast cells have recently been shown to interact with certain pathogenic bacteria and present microbial antigens to the immune system. We show here that Bordetella pertussis can adhere to and be phagocytosed by ... Full text Link to item Cite

Mast cell modulation of immune responses to bacteria.

Journal Article Immunol Rev · February 2001 Mast cells are key elements of the immune system. These cells release a wide variety of pro-inflammatory mediators which are responsible for the pathophysiology of many allergic diseases. Recent studies, however, have shown that mast cells have the capacit ... Full text Link to item Cite

Co-option of endocytic functions of cellular caveolae by pathogens.

Journal Article Immunology · January 2001 Featured Publication It is increasingly becoming clear that various immune cells are infected by the very pathogens that they are supposed to attack. Although many mechanisms for microbial entry exist, it appears that a common route of entry shared by certain bacteria, viruses ... Full text Link to item Cite

Involvement of cellular caveolae in bacterial entry into mast cells.

Journal Article Science · August 4, 2000 Featured Publication Caveolae are subcellular structures implicated in the import and transcytosis of macromolecules and in transmembrane signaling. To date, evidence for the existence of caveolae in hematopoietic cells has been ambiguous. Caveolae were detected in the microvi ... Full text Link to item Cite

Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis.

Journal Article J Leukoc Biol · June 2000 Stimulated mast cells release a variety of chemotactic factors such as tumor necrosis factor alpha (TNF-alpha) and leukotriene B4. Recent studies have shown that mast cell-derived TNF-alpha plays a critical role in host defense against Gram negative bacter ... Full text Link to item Cite

Molecular mechanisms for the diversification of bacterial surface lectins.

Journal Article ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 26, 2000 Link to item Cite

Normal neutrophil function in cathepsin G-deficient mice.

Journal Article Blood · December 15, 1999 Cathepsin G is a neutral serine protease that is highly expressed at the promyelocyte stage of myeloid development. We have developed a homologous recombination strategy to create a loss-of-function mutation for murine cathepsin G. Bone marrow derived from ... Link to item Cite

Internalization of FimH+ Escherichia coli by the human mast cell line (HMC-1 5C6) involves protein kinase C.

Journal Article J Leukoc Biol · December 1999 Rodent mast cells (MC) play critical roles in host defense against bacterial infection. However, bacteria-mediated signaling mechanisms in MC have not been studied. In addition, the response of human MC to bacteria is not fully investigated. This study exa ... Full text Link to item Cite

Nonopsonic FIMH-Mediated phagocytosis of E. coli and its possible contribution to recurrent urinary tract infections

Journal Article Advances in Cellular and Molecular Biology of Membranes and Organelles · December 1, 1999 Full text Cite

Bacteria-host cell interaction mediated by cellular cholesterol/glycolipid-enriched microdomains.

Journal Article Biosci Rep · October 1999 Gram negative bacterial infection is a leading cause of fatality and is attributed, at least in part, to the bacteria's capacity to persist in the host in spite of appropriate antibiotic therapy. It has been suggested that bacteria evade antibiotics by hid ... Full text Link to item Cite

Inability of encapsulated Klebsiella pneumoniae to assemble functional type 1 fimbriae on their surface.

Journal Article FEMS Microbiol Lett · October 1, 1999 We screened phase variants of Klebsiella pneumoniae isolates for the expression of capsule and type 1 fimbriae and found that all of the 22 blood isolates were encapsulated and did not express type 1 fimbriae while 10 of 11 urinary tract isolates expressed ... Full text Link to item Cite

The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48.

Journal Article Proc Natl Acad Sci U S A · July 6, 1999 Featured Publication Mast cells are well known for their harmful role in IgE-mediated hypersensitivity reactions, but their physiological role remains a mystery. Several recent studies have reported that mast cells play a critical role in innate immunity in mice by releasing t ... Full text Link to item Cite

Production of TNF-alpha by murine bone marrow derived mast cells activated by the bacterial fimbrial protein, FimH.

Journal Article Clin Immunol · March 1999 Production of tumor necrosis factor alpha (TNF-alpha) by mast cells is an important aspect of host defense against gram negative bacteria. In order to define the intracellular pathways utilized by mast cells in this physiological, protective role, we have ... Full text Link to item Cite

Molecular basis for the enterocyte tropism exhibited by Salmonella typhimurium type 1 fimbriae.

Journal Article J Biol Chem · February 26, 1999 Featured Publication Salmonella typhimurium exhibits a distinct tropism for mouse enterocytes that is linked to their expression of type 1 fimbriae. The distinct binding traits of Salmonella type 1 fimbriae is also reflected in their binding to selected mannosylated proteins a ... Full text Link to item Cite

Bacterial up-take by human mast cells require protein kinase C.

Journal Article JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1999 Link to item Cite

Phagocytic and tumor necrosis factor alpha response of human mast cells following exposure to gram-negative and gram-positive bacteria.

Journal Article Infect Immun · December 1998 Recent studies have implicated rodent mast cells in the innate immune response to infectious bacteria. We report that cord blood-derived human mast cells (CBHMC) obtained from culture of cord blood progenitors phagocytozed and killed various gram-negative ... Full text Link to item Cite

Mast cells and basophils in innate immunity.

Journal Article Semin Immunol · October 1998 Mast cells and basophils are primarily associated with the pathophysiology of allergic diseases. Considering that these cells have been preserved through evolution they must serve a valuable function. Intrinsically, mast cells are ideally placed and well e ... Full text Link to item Cite

Clinical implications of mast cell-bacteria interaction.

Journal Article J Mol Med (Berl) · August 1998 Mast cells are traditionally known for mediating allergic reactions. In addition, these cells have been implicated in the pathogenesis of a variety of clinical conditions such as atopic and contact dermatitis, bullous pemphigoid, fibrotic lung disease, neu ... Full text Link to item Cite

Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis.

Journal Article Nat Med · May 1998 Featured Publication Neutrophil elastase (NE) is a potent serine proteinase whose expression is limited to a narrow window during myeloid development. In neutrophils, NE is stored in azurophil granules along with other serine proteinases (cathepsin G, proteinase 3 and azurocid ... Full text Link to item Cite

Fimbriae-mediated host-pathogen cross-talk.

Journal Article Curr Opin Microbiol · February 1998 Recent studies show that the coupling of fimbrial adhesins of uropathogenic Escherichia coli and pathogenic Neisseria species to their complementary receptors on host cells is a dynamic event, involving specific signaling to the bacteria as well as to the ... Full text Link to item Cite

Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic.

Journal Article Nature · October 9, 1997 Featured Publication Strains of Escherichia coli persist within the human gut as normal commensals, but are frequent pathogens and can cause recurrent infection. Here we show that, in contrast to E. coli subjected to opsonic interactions stimulated by the host's immune respons ... Full text Link to item Cite

Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection.

Journal Article J Clin Invest · September 1, 1997 Featured Publication The FimH subunit of type 1-fimbriated Escherichia coli has been implicated as an important determinant of bacterial adherence and colonization of the urinary tract. Here, we sought to localize the functionally important domain(s) within the FimH molecule a ... Full text Link to item Cite

Mast cells in infection and immunity.

Journal Article Infect Immun · September 1997 Full text Link to item Cite

Mast cells as modulators of host defense in the lung.

Journal Article Front Biosci · February 15, 1997 Mast cells display a distinct spatial distribution in the lung where they are found preferentially in intraepithelial locations or in deeper tissue around blood vessels, bronchioles and mucus secreting glands. Yet the physiological role of these granule-la ... Full text Link to item Cite

Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha.

Journal Article Nature · May 2, 1996 Featured Publication Although mast cells have been implicated in a variety of inflammatory conditions including immediate hypersensitivity and interstitial cystitis, their physiological role in the body is unknown. We investigated the role of mast cells in host defence against ... Full text Link to item Cite

Mast cells process bacterial Ags through a phagocytic route for class I MHC presentation to T cells.

Journal Article J Immunol · February 15, 1996 The pivotal role of mast cells in allergic reactions and inflammatory processes is well established and recent studies have suggested that mast cells may also have a role in specific immune responses. Because mast cells have been shown to phagocytose and k ... Link to item Cite

Bacteria--Mast Cell Interactions in Inflammatory Disease.

Journal Article Am J Ther · October 1995 Chronic inflammatory diseases of the gastrointestinal tract such as ulcerative colitis and Crohn's disease are characterized by mast cell proliferation and secretion of inflammatory mediators. The determinant(s) responsible for stimulating mast cells in th ... Full text Link to item Cite

FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae.

Journal Article Proc Natl Acad Sci U S A · March 14, 1995 Featured Publication Type 1 pili are heteropolymeric mannosebinding fibers produced by all members of the Enterobacteriaceae family. The bulk of the fiber is composed of FimA. Two macromolecular complexes responsible for mediating an interaction with mannose-containing recepto ... Full text Link to item Cite

Interaction of bacteria with mast cells.

Journal Article Methods Enzymol · 1995 Full text Link to item Cite

The PapG tip adhesin of P fimbriae protects Escherichia coli from neutrophil bactericidal activity.

Journal Article Infect Immun · December 1994 Compared with Escherichia coli ORN103, a nonfimbriated K-12 strain, P-fimbriated E. coli ORN103/pPAP5 was found to interact poorly with human neutrophils and resist their bactericidal activity in vitro. PapG, the Gal alpha(1-->4)Gal binding moiety located ... Full text Link to item Cite

Mast cell degranulation induced by type 1 fimbriated Escherichia coli in mice.

Journal Article J Clin Invest · April 1994 Featured Publication The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may play a pivotal role in host defense against bacterial infection. The ability of the opp ... Full text Link to item Cite

Type 1 fimbrial shafts of Escherichia coli and Klebsiella pneumoniae influence sugar-binding specificities of their FimH adhesins.

Journal Article Infect Immun · March 1994 The type 1 fimbriae of enterobacteria comprise FimA, which constitutes most of the fimbrial shaft, and a cassette of three minor ancillary subunits including FimH, the mannose-binding moiety. The sugar-binding specificities of Escherichia coli and Klebsiel ... Full text Link to item Cite

Mast cell phagocytosis of FimH-expressing enterobacteria.

Journal Article J Immunol · February 15, 1994 Most studies of mast cells have been directed at their role in the pathophysiology of IgE-mediated allergic reactions with little recognition of their participation in bacterial infections. We report that mast cells can specifically bind FimH, a mannose-bi ... Link to item Cite

Bactericidal activity of mast cells

Journal Article Gastroenterology · January 1, 1994 Full text Cite

Bactericidal activity of mast cells

Journal Article Gastroenterology · 1994 Cite

FimC is a periplasmic PapD-like chaperone that directs assembly of type 1 pili in bacteria.

Journal Article Proc Natl Acad Sci U S A · September 15, 1993 Featured Publication Biogenesis of the type 1 pilus fiber in Escherichia coli requires the product of the fimC locus. We have demonstrated that FimC is a member of the periplasmic chaperone family. The deduced primary sequence of FimC shows a high degree of homology to PapD an ... Full text Link to item Cite

Neutrophil activation by nascent FimH subunits of type 1 fimbriae purified from the periplasm of Escherichia coli.

Journal Article J Biol Chem · February 5, 1993 Previous studies of type 1 fimbriae of Escherichia coli have implicated FimH, a minor subunit, as the determinant of its mannose binding property. Structure-function analysis of FimH has not been possible because of the difficulty in obtaining adequate amo ... Link to item Cite

T-cell-independent stimulation of immunoglobulin secretion in resting human B lymphocytes by the mannose-specific adhesin of Escherichia coli type 1 fimbriae.

Journal Article Infect Immun · December 1992 Purified Escherichia coli type 1 fimbriae have been shown previously to stimulate T-cell-independent proliferation of human B lymphocytes. The response is mediated by the mannose-specific, lectin-like adhesin protein FimH. Here we show that type 1 fimbriae ... Full text Link to item Cite

Functional heterogeneity of type 1 fimbriae of Escherichia coli.

Journal Article Infect Immun · November 1992 Escherichia coli and other members of the family Enterobacteriaceae express surface fibrillar structures, fimbriae, that promote bacterial adhesion to host receptors. Type 1 fimbriae possess a lectinlike component, FimH, that is commonly thought to cause b ... Full text Link to item Cite

Glycerol-induced unraveling of the tight helical conformation of Escherichia coli type 1 fimbriae.

Journal Article J Bacteriol · August 1992 Glycerol was found to unravel the helical conformation of Escherichia coli type 1 fimbriae without appreciable depolymerization. The linearized fimbrial polymers have a diameter of 2 nm, react strongly with a monoclonal antibody directed at an inaccessible ... Full text Link to item Cite

Fragmentation of Escherichia coli type 1 fimbriae exposes cryptic D-mannose-binding sites.

Journal Article J Bacteriol · July 1991 Cells of the gram-negative bacterium Escherichia coli are able to attach to various host cells by means of a mannose-specific adhesin associated with type 1 fimbriae. Here we show that fragmentation of type 1 fimbriae by freezing and thawing results in inc ... Full text Link to item Cite

Isolation and characterization of a 180-kiloDalton salivary glycoprotein which mediates the attachment of Actinomyces naeslundii to human buccal epithelial cells.

Journal Article J Periodontal Res · March 1991 The adherence of Actinomyces naeslundii to human buccal mucosa is mediated by specific interactions between the bacterial cell surface fimbriae and complementary beta-linked galactoside receptors on the epithelial cell surface. The buccal mucosa and the ba ... Full text Link to item Cite

Chaperone-assisted assembly and molecular architecture of adhesive pili.

Journal Article Annu Rev Microbiol · 1991 The assembly of bacterial pili as exemplified here by P and type 1 pili of E. coli is a complex process involving specific molecular interactions between structural and chaperone proteins. The assembly process occurs postsecretionally, i.e. after the subun ... Full text Link to item Cite

Colonial morphology of staphylococci on Memphis agar: phase variation of slime production, resistance to beta-lactam antibiotics, and virulence.

Journal Article J Infect Dis · June 1990 The growth of Staphylococcus epidermidis sensu stricto and Staphylococcus saprophyticus on Memphis agar yielded up to 6 morphotypes with each strain. With S. epidermidis, one morphotype produced slime (rho) but became non-slime-producing (epsilon) at a hig ... Full text Link to item Cite

Structure and orientation of expressed bovine coronavirus hemagglutinin-esterase protein

Journal Article Journal of Virology · 1990 The sequence of the hemagglutinin-esterase (HE) gene for the Mebus strain of bovine coronavirus was obtained from cDNA clones, and its deduced product is a 47,700-kilodalton apoprotein of 424 amino acids. Expression of the HE protein in vitro in the presen ... Cite

Mitogenic stimulation of human B lymphocytes by the mannose-specific adhesin on Escherichia coli type 1 fimbriae.

Journal Article J Immunol · February 1, 1989 Escherichia coli type 1 fimbriae contain in association with the major structural protein a lectin-like adhesin moiety that mediates attachment of E. coli to mannose-containing receptors on the surface of host cells. We have investigated the lymphocyte mit ... Link to item Cite

Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae.

Journal Article Nature · December 15, 1988 Featured Publication A variety of genera and species of the family Enterobacteriaceae bear surface fimbriae that enable them to bind to D-mannose residues on eukaryotic cells. Until recently, it was thought that the D-mannose binding site was located in the major structural su ... Full text Link to item Cite

Bacterial adherence. Adhesin receptor-mediated attachment of pathogenic bacteria to mucosal surfaces.

Journal Article Am Rev Respir Dis · December 1988 Pathogenic bacteria adhere to and colonize mucosal surfaces of the susceptible host in a highly selective manner. After the organisms penetrate the nonspecific mechanical and cleansing forces, ligands (or adhesins) on the surface of the bacteria interact i ... Full text Link to item Cite

Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli.

Journal Article Antimicrob Agents Chemother · August 1988 We investigated the influence of berberine sulfate, an ancient Chinese antibiotic, upon the adhesion of uropathogenic Escherichia coli to erythrocytes and epithelial cells. Although berberine sulfate in increasing concentrations had no effect on bacterial ... Full text Link to item Cite

Hyperadhesive mutant of type 1-fimbriated Escherichia coli associated with formation of FimH organelles (fimbriosomes).

Journal Article Infect Immun · May 1988 The relationships of the genes and gene-products mediating D-mannose-specific attachment of type 1 fimbriae of Escherichia coli to eucaryotic cells were investigated by deletion mutation analysis of recombinant plasmid pSH2, which carries the genetic infor ... Full text Link to item Cite

Isolation and characterization of a receptor for type 1 fimbriae of Escherichia coli from guinea pig erythrocytes.

Journal Article J Biol Chem · April 15, 1988 The adhesion of Escherichia coli to eukaryotic cells is mediated by proteinaceous surface appendages called fimbriae and complementary receptors on host cells. Although type 1 fimbriae, which contain a D-mannose-reactive lectin, have been well studied litt ... Link to item Cite

Binding of bacteria to mucosal surfaces.

Journal Article Monogr Allergy · 1988 Link to item Cite

Identification of two ancillary subunits of Escherichia coli type 1 fimbriae by using antibodies against synthetic oligopeptides of fim gene products.

Journal Article J Bacteriol · December 1987 We have chemically synthesized oligopeptides corresponding to the NH2-terminal stretch of two gene products, designated FimG and FimH, of the fim gene cluster of Escherichia coli. These synthetic peptides, designated S-T1FimG(1-16) and S-T1FimH(1-25)C, evo ... Full text Link to item Cite

Assembly of a chemically synthesized peptide of Escherichia coli type 1 fimbriae into fimbria-like antigenic structures.

Journal Article J Bacteriol · June 1987 Escherichia coli type 1 fimbriae are composed of subunits, each of which comprises 158 amino acids. We synthesized a copy of a 13-residue peptide, located near the NH2 terminus of the fimbrial subunit, that assumed some of the properties of type 1 fimbriae ... Full text Link to item Cite

Use of monoclonal antibodies to probe subunit- and polymer-specific epitopes of 987P fimbriae of Escherichia coli.

Journal Article Infect Immun · April 1987 The relationship between the structure and biological function of 987P fimbriae of a strain of enterotoxigenic Escherichia coli (O9:K103:H-) from piglets was investigated. A set of four monoclonal antibodies was prepared from the spleen cells of mice immun ... Full text Link to item Cite

Interaction of a 60-kilodalton D-mannose-containing salivary glycoprotein with type 1 fimbriae of Escherichia coli.

Journal Article Infect Immun · October 1986 A 60-kilodalton glycoprotein previously isolated and purified from human saliva (J. B. Babu, E. H. Beachey, D. L. Hasty, and W. A. Simpson, Infect. Immun. 51: 405-413, 1986) was found to interact with type 1 fimbriae and prevent adhesion of type 1 fimbriat ... Full text Link to item Cite

Influence of trimethoprim and sulfamethoxazole on the synthesis, expression, and function of type 1 fimbriae of Escherichia coli.

Journal Article J Infect Dis · September 1986 We investigated the effects of low levels of sulfamethoxazole and trimethoprim on biosynthesis, expression at the cell surface, and hemagglutinating activity of type 1 fimbriae from a urinary tract isolate of Escherichia coli. The mannose-sensitive hemaggl ... Full text Link to item Cite

The genetic determinant of adhesive function in type 1 fimbriae of Escherichia coli is distinct from the gene encoding the fimbrial subunit.

Journal Article J Bacteriol · March 1986 The role of type 1 fimbriae in the mannose-sensitive attachment of Escherichia coli to eucaryotic cells was investigated by deletion mutation analysis of a recombinant plasmid, pSH2, carrying the genetic information for the synthesis and expression of func ... Full text Link to item Cite

Protection against Escherichia coli-induced urinary tract infections with hybridoma antibodies directed against type 1 fimbriae or complementary D-mannose receptors.

Journal Article Infect Immun · June 1985 Hybridoma antibodies directed against quaternary structural epitopes of the type 1 fimbrial adhesin of Escherichia coli or against D-mannose, the sugar determinant in the complementary host cell receptor, prevented the attachment of mannose-sensitive E. co ... Full text Link to item Cite

Antiadhesive properties of a quaternary structure-specific hybridoma antibody against type 1 fimbriae of Escherichia coli.

Journal Article J Exp Med · October 1, 1983 The relationship between the structure and biological function of type 1 fimbriae of Escherichia coli was investigated using a set of monoclonal antibodies directed against conformation-specific antigenic determinants. Of three monoclonal antibodies tested ... Full text Link to item Cite

Adherence of streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa to fibronectin-coated and uncoated epithelial cells.

Journal Article Infect Immun · September 1983 The relationship between the variability in the fibronectin (Fn) content on human buccal epithelial cells and the capacity of the cells to bind gram-positive (Streptococcus pyogenes) or gram-negative (Escherichia coli or Pseudomonas aeruginosa) bacteria wa ... Full text Link to item Cite

Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1.

Journal Article J Immunol · May 1983 We describe the production of the monoclonal antibody B73.1, reacting with a subset of human lymphocytes and, in about one-half of the donors, with neutrophilic polymorphonuclear leukocytes. In the peripheral blood from normal adult donors, 14.6 +/- 8.5% o ... Link to item Cite

A comparative study of the mannose-resistant and mannose-sensitive haemagglutinins of Escherichia coli isolated from urinary tract infections.

Journal Article Infection · 1983 The distribution of mannose-resistant (MRHA) and mannose-sensitive (MSHA) fimbrial haemagglutinins was examined in 482 strains of Escherichia coli isolated from 390 adult women and 45 pregnant mothers with a variety of urinary tract infections (UTI), and f ... Full text Link to item Cite

Incidence of free-living amoebae in the nasal passages of local population in Zaria, Nigeria.

Journal Article J Trop Med Hyg · October 1982 Following the observation of cases of primary amoebic meningoencephalitis (PAME) during the dusty harmattan period in Zaria, a survey was carried out in randomly selected local populations of Zaria, to find out the incidence of free-living amoebae in the n ... Link to item Cite

Recovery of soil Amebas from the nasal passages of children during the dusty harmattan period in Zaria.

Journal Article Am J Clin Pathol · February 1979 Following a fatal case of primary amebic meningoencephalitis during the dusty harmattan period in an 8-month-old child in whose case Naegleria fowleri was recovered both from the cerebrospinal fluid and from material from the nose in absence of a history o ... Full text Link to item Cite