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Neutrophil IFN-gamma in host defense and inflammation

中性粒细胞 IFN-γ 在宿主防御和炎症中的作用

基本信息

批准号：
9106433
负责人：
Felix Yarovinsky
金额：
$ 44.99万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9106433
关键词：
Address Animals Blood Bone Marrow Cells Cytoplasmic Granules Development Disease Event Goals Health Host Defense Host resistance Human Human Genome Immune Immune response Immune system Immunity Infection Inflammation Interferon Type II Interferons Interleukin-12 Knowledge Lymphoid Cell Mediating Microbe Modeling Mus Mycobacterium tuberculosis Natural Killer Cells Neuraxis Parasites Phase Physiological Play Population Production Pseudogenes Recruitment Activity Regulation Resistance to infection Risk Role Salmonella typhimurium Site Source Streptococcus pneumoniae T-Lymphocyte Testing Toll-like receptor 11 Toll-like receptors Toxoplasma gondii Toxoplasmosis adaptive immunity arm cytokine innovation insight macrophage microbial neutrophil novel novel strategies pathogen precursor cell profilin response seropositive transcription factor

项目摘要

DESCRIPTION (provided by applicant): IFN- is a key cytokine that mediates host resistance to a variety of intracellular pathogen. Until recently, it was largely acknowledged that lymphoid cells are the sole sources for IFN-. We have recently established that neutrophils are an emerging cellular source of IFN-, a key cytokine that mediates host defense to Toxoplasma gondii and other intracellular pathogens. Production of IFN-by neutrophils, in contrast to lymphoid cells, is Toll-like receptor (TLR) and IL-12-independent and the events associated with IFN- production by neutrophils are not understood. We have also observed that neutrophils express IFN-during their lineage development in the bone marrow niche independently of microbes. IFN- accumulates in neutrophilic granules and is released upon induction of neutrophil degranulation. We propose to build upon these findings to gain a deeper understanding of how neutrophil-derived IFN- expression is regulated, and to investigate the physiological significance of neutrophil-derived IFN- in mouse and human models of toxoplasmosis. In Aim 1, we will identify neutrophil precursors involved in IFN- production in naïve and Toxoplasma gondii-infected mice and determine the transcription factors that regulate IFN- production in human and mouse neutrophil. In Aim 2, we will use mice harboring neutrophil-specific IFN- deficiency to test the hypothesis that neutrophil-derived IFN-coordinates innate and adaptive immune responses to Toxoplasma gondii. These studies will advance our understanding of how human and mouse innate immune systems