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Role of eosinophils during bacterial infection

嗜酸性粒细胞在细菌感染过程中的作用

基本信息

批准号：
10728101
负责人：
Denise M Monack
金额：
$ 19.59万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-14 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10728101
关键词：
Acute Affect Anti-Bacterial Agents Antimicrobial Effect B-Lymphocytes Bacteria Bacterial Infections Biochemical CCL11 gene Cells Chemotactic Factors Chronic Citrobacter rodentium Complex Cues Cytoplasmic Granules DNA Data Disease Environment Eotaxin Future Gastroenteritis Genetic Goals Granuloma Growth Health Helicobacter pylori Helminths Homeostasis Host resistance Hypersensitivity IgG2 Immune Immune response Immunity Infection Infectious granuloma Inflammatory Interferon Type II Knowledge Leukocytes Lung Macrophage Modeling Mus Mycobacterium tuberculosis Oranges Patients Phase Predisposition Preventive Production Property Proteins Pseudomonas aeruginosa Publishing Regulation Reporting Role Salmonella Salmonella enterica Salmonella infections Salmonella typhimurium Staphylococcus aureus Stomach Systemic infection T-Lymphocyte T-Lymphocyte Subsets Testing Therapeutic Tissues Tuberculosis Typhoid Fever Virulence Factors Virus allergic response antimicrobial bactericide chemokine chronic infection eosinophil extracellular helminth infection immunoregulation in vivo insight mesenteric lymph node nonhuman primate pathogen pathogenic bacteria persistent bacterial infection pharmacologic response tuberculosis granuloma wound healing

项目摘要

Project Summary Influx of eosinophils is typically associated with type II responses during allergy. More recent reports indicate that eosinophils have essential immunoregulatory roles, as well as key anti-microbial effects against helminths, viruses, and some bacterial species. However, the mechanisms underlying how eosinophils contribute to eliminating bacteria are understudied, and results are diametrically different depending upon the infecting pathogen and in acute versus chronic infection. In this application, we propose to investigate the role of eosinophils during persistent Salmonella infection within mesenteric lymph nodes (MLNs) of 129X1/Sv/J mice. Our unpublished data show that eosinophils, which we have localized to STm-containing granulomas, increased significantly over the first 8 weeks of Salmonella enterica Typhimurium (STm) infection, correlated with an increase in the eosinophil chemoattractant CCL11. In addition, depletion of eosinophils in STm-infected mice rendered mice more susceptible to infection. Importantly, eosinophil-depleted mice had a significant reduction of IFNγ-producing cells and lower tissue levels of IFNγ compared to IgG2 controls, suggesting that eosinophils contribute to pathogen control by influencing the granuloma microenvironment to be Th1 skewed. Our central hypothesis is that the functions of eosinophils within infected tissues are regulated by microenvironments, such as the granuloma, and function to contain the pathogen during persistent infection. The impact of eosinophils on granuloma formation and pathogen control via the production of extracellular DNA traps and possible manipulation by bacterial virulence factors will be investigated (Aim 1). In addition, we will characterize the immunoregulatory effector functions of eosinophils during STm persistence in the MLNs (Aim 2).

项目总结