Journal ArticleInfect Immun · October 15, 2024
Naegleria fowleri (N. fowleri) infection via the upper respiratory tract causes a fatal CNS disease known as primary amoebic meningoencephalitis (PAM). The robust in vivo immune response to N. fowleri infection underlies the immunopathology that characteri ...
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Journal ArticleMucosal immunology · October 2024
The olfactory mucosa is important for both the sense of smell and as a mucosal immune barrier to the upper airway and brain. However, little is known about how the immune system mediates the conflicting goals of neuronal maintenance and inflammation in thi ...
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Journal ArticleCell Death Dis · June 10, 2024
Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tu ...
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Journal ArticleNat Rev Immunol · June 2024
The olfactory mucosa is a component of the nasal airway that mediates the sense of smell. Recent studies point to an important role for the olfactory mucosa as a barrier to both respiratory pathogens and to neuroinvasive pathogens that hijack the olfactory ...
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Journal ArticleJ Exp Med · February 5, 2024
The central nervous system (CNS) tightly regulates access of circulating immune cells. Immunosurveillance is therefore managed in the meninges at the borders of the CNS. Here, we demonstrated that mural cells, which include pericytes and smooth muscle cell ...
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Journal ArticleCell Mol Immunol · February 2024
Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier. Situated in the nasal passages, the olfactory mucosa is directly exposed to the en ...
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Journal ArticleProc Natl Acad Sci U S A · January 2, 2024
Phylogenetically and antigenically distinct influenza A and B viruses (IAV and IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved in both IAV and IBV hemagglutinins (HAs) could protect against d ...
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Journal ArticleFront Cell Infect Microbiol · 2024
The free-living amoeba Naegleria fowleri (NF) causes a rare but lethal parasitic meningoencephalitis (PAM) in humans. Currently, this disease lacks effective treatments and the specific molecular mechanisms that govern NF pathogenesis and host brain respon ...
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Journal ArticleMethods Mol Biol · 2023
Olfactory immunology is an emerging field in the context of infectious disease and neuroimmunology, yet characterization of immune cells within the murine olfactory mucosa remains sparse. This is partially due to the difficulty in distinguishing olfactory- ...
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Journal ArticleSci Transl Med · December 21, 2022
SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy st ...
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Journal ArticleImmunity · November 8, 2022
While blood antibodies mediate protective immunity in most organs, whether they protect nasal surfaces in the upper airway is unclear. Using multiple viral infection models in mice, we found that blood-borne antibodies could not defend the olfactory epithe ...
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Journal ArticleElife · May 5, 2022
Central nervous system (CNS) infections are a major cause of human morbidity and mortality worldwide. Even patients that survive, CNS infections can have lasting neurological dysfunction resulting from immune and pathogen induced pathology. Developing appr ...
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Journal ArticleNature immunology · May 2022
T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching corecepto ...
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Journal ArticlebioRxiv · April 18, 2022
Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acu ...
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Journal ArticleJ Clin Invest · February 15, 2022
BACKGROUNDPresbyosmia, or aging-related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction and is subject ...
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Journal ArticleFront Trop Dis · 2022
Naegleria fowleri, or the "brain-eating amoeba," is responsible for a rare, but lethal, infection known as primary amoebic meningoencephalitis (PAM). Confirmed PAM cases have seen both a rise in numbers, as well as expansion of geographic range over the pa ...
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Journal ArticleNat Immunol · March 2021
During chronic infection and cancer, a self-renewing CD8+ T cell subset maintains long-term immunity and is critical to the effectiveness of immunotherapy. These stem-like CD8+ T cells diverge from other CD8+ subsets early after chronic viral infection. Ho ...
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Journal ArticleCell Rep · September 1, 2020
Influenza viruses initiate infection in the upper respiratory tract (URT), but early viral tropism and the importance of cell-type-specific antiviral responses in this tissue remain incompletely understood. By infecting transgenic lox-stop-lox reporter mic ...
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Journal ArticleSci Immunol · June 5, 2020
The neuroepithelium is a nasal barrier surface populated by olfactory sensory neurons that detect odorants in the airway and convey this information directly to the brain via axon fibers. This barrier surface is especially vulnerable to infection, yet resp ...
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Journal ArticleImmunity · March 17, 2020
Intrinsic complement C3 activity is integral to human T helper type 1 (Th1) and cytotoxic T cell responses. Increased or decreased intracellular C3 results in autoimmunity and infections, respectively. The mechanisms regulating intracellular C3 expression ...
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Journal ArticleCell · August 22, 2019
Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restric ...
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Journal ArticleNat Immunol · July 2019
Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription fa ...
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Journal ArticleImmunity · December 20, 2016
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Infections induce pathogen-specific T cell differentiation into diverse effectors (Teff) that give rise to memory (Tmem) subsets. The cell-fate decisions and lineage relationships that underlie these transitions are poorly understood. Here, we found that t ...
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Journal ArticleCell Rep · September 29, 2015
T follicular helper (TFH) and T helper 1 (Th1) cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these tw ...
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Journal ArticleJournal of Immunology · December 1, 2013
Recognition of microbial components is critical for activation of TLRs, subsequent innate immune signaling, and directing adaptive immune responses. The DNA sensor TLR9 traffics from the endoplasmic reticulum to endolysosomal compartments where it is cleav ...
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Journal ArticleCell Rep · October 31, 2013
Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, prot ...
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Journal ArticleImmunol Rev · September 2013
The fate of T lymphocytes revolves around a continuous stream of interactions between the T-cell receptor (TCR) and peptide-major histocompatibility complex (MHC) molecules. Beginning in the thymus and continuing into the periphery, these interactions, ref ...
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Journal ArticleImmunity · March 23, 2012
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Neutralizing antibodies have been thought to be required for protection against acutely cytopathic viruses, such as the neurotropic vesicular stomatitis virus (VSV). Utilizing mice that possess B cells but lack antibodies, we show here that survival upon s ...
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Journal ArticleNat Immunol · December 2010
Hepatic natural killer (NK) cells mediate antigen-specific contact hypersensitivity (CHS) in mice deficient in T cells and B cells. We report here that hepatic NK cells, but not splenic or naive NK cells, also developed specific memory of vaccines containi ...
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Journal ArticleNature · June 24, 2010
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Lymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) ...
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Journal ArticleBlood · June 17, 2010
Chronic lymphocytic leukemia (CLL) is the most prevalent human leukemia and is characterized by the progressive accumulation of long-lived malignant B cells. Here we show that human B-CLL cells selectively express high levels of Toll-like receptor 9 (TLR9) ...
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Journal ArticleNanomedicine (Lond) · February 2010
Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus devel ...
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Journal ArticleCell · November 30, 2007
Constitutive egress of bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) into the blood is a well-established phenomenon, but the ultimate fate and functional relevance of circulating HSPCs is largely unknown. We show that mouse tho ...
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Journal ArticleACS Chem Biol · November 20, 2007
Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine i ...
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Journal ArticleNature · November 1, 2007
Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is uncl ...
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Journal ArticleJ Virol · April 2007
Early control of virus replication by the innate immune response is essential to allow time for the generation of a more effective adaptive immune response. As an important component of innate immunity, complement has been shown to be necessary for protect ...
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Journal ArticleJ Immunol · October 1, 2004
Plasmacytoid dendritic cells (PDCs) are key effectors in host innate immunity and orchestrate adaptive immune responses. CpG oligodeoxynucleotides (ODN) have potent immunostimulatory effects on PDCs through TLR9 recognition and signaling. Little is known a ...
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