Scholars@Duke
Soman Ninan Abraham

Soman Ninan Abraham

Grace Kerby Distinguished Professor of Pathology
Pathology
Duke Box 3172, Durham, NC 27710
257 Jones Bldg, Durham, NC 27710

Featured Works

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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

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

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

Journal article Science · August 24, 2001 Featured Publication 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

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

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

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

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

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 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

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

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

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

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