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Natural killer cell receptor-expressing B cells as regulators of mucosal immunity in SIV infection

表达自然杀伤细胞受体的 B 细胞作为 SIV 感染粘膜免疫的调节剂

基本信息

批准号：
9927204
负责人：
Roger Keith Reeves
金额：
$ 21万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-23 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9927204
关键词：
Acquired Immunodeficiency Syndrome Acute Adaptive Immune System Antiviral Agents Autoimmune Diseases B-Lymphocytes Biological Markers Cells Cellular Assay Characteristics Chronic Colon Communicable Diseases Custom Cytometry Data Data Analyses Disease Genetic Transcription HIV HIV Infections Health Human Immune Immunoglobulin A Immunoglobulin M Immunologics Immunotherapeutic agent Infection Inflammasome Innate Immune Response Innate Immune System Interleukin-12 Interleukin-18 Knowledge Lentivirus Infections Lymphocyte Lymphoid Macaca mulatta Mediating Mediator of activation protein Memory Metabolic Modeling Mucosal Immune Responses Mucosal Immunity Mucous Membrane Mus Myeloid Cells Natural Immunity Natural Killer Cells Neighborhoods Outcome Pathogenicity Pathway interactions Peripheral Blood Mononuclear Cell Phenotype Play Population Prevention strategy Primates Production Publishing Receptor Cell Receptors, Antigen, B-Cell Role SIV Sampling Source Spleen Surface Testing Therapeutic Tissues Training Vaccination Vaccines Virus Virus Diseases adaptive immune response adaptive immunity base cell type chronic infection cross reactivity cytokine drug development first responder gastrointestinal innate immune function insight macrophage mast cell monocyte mucosal site natural antibodies neutrophil new therapeutic target nonhuman primate novel pathogen phenotypic data rectal response transcriptomics transmission process vaccine efficacy vaginal mucosa

项目摘要

PROJECT SUMMARY Recently, a seemingly novel innate immune cell subset bearing features of natural killer (NK) and B cells was identified in mice. So-called NKB cells appear as first responders to viral infections at mucosal surfaces, but the full functional niche remains unknown and prior to our recent studies it has been unclear if these cells existed in higher order primates. In our recently published findings (Manickam et al., AIDS 2018) and new preliminary data we found that phenotypically analogous populations of NKB cells can be found systemically in humans and non-human primates, but are enriched in spleen, similar to mice. Furthermore, NKB cells had stable surface expression of non-secreted IgM and IgA, and are massively expanded in colonic tissues during chronic SIV infection. In this new proposal we will rigorously test we will test the overarching hypothesis that NKB cells are early responders at mucosal sites of infection and activation of this cell type is critical to initiate anti- HIV/SIV innate immune responses through two focused specific aims: (1) Identify transcriptomic and functional signatures of NKB cells under homeostatic conditions; and (2) Identify the role(s) and functional significance of mucosal NKB cells in SIV infection. The outcomes of this proposal will provide the first detailed analyses of NKB cells during lentivirus infection and potentially means to target these unique cells for immunotherapeutics or vaccine strategies.

项目总结