Role of eosinophils during bacterial infection

嗜酸性粒细胞在细菌感染过程中的作用

• 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
• 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

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 Our unpublished data show that eosinophils, which we have localized to STm-containing granulomas, increased significantly over the first 8 weeks of Salmonella enterica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).

项目摘要 嗜酸性粒细胞的涌入通常与过敏过程中II型反应有关。最新报告表明 嗜酸性粒细胞具有必不可少的免疫调节作用，以及针对蠕虫的关键抗菌作用 病毒和一些细菌。但是，嗜酸性粒细胞如何促进的机制 消除细菌是被理解的，结果取决于感染 病原体，急性与慢性感染。在此应用中，我们建议调查 129x1/sv/j小鼠的肠系膜淋巴结（MLN）内持续的沙门氏菌感染期间的嗜酸性粒细胞。 我们未发表的数据表明，嗜酸性粒细胞（我们本地化为含STM的肉芽肿）增加了 在沙门氏菌鼠伤寒沙门氏菌（STM）感染的前8周中，与 嗜酸性粒细胞趋化剂CCL11的增加。另外，嗜酸性粒细胞在STM感染的小鼠中的耗竭 使小鼠更容易感染。重要的是，嗜酸性粒细胞的小鼠显着降低 与IgG2对照相比 通过影响肉芽瘤微环境偏向于病原体控制的贡献。我们的中心 假设是，感染组织中嗜酸性粒细胞的功能受到微环境的调节，这样 作为肉芽瘤，并在持续感染过程中含有病原体的功能。嗜酸性粒细胞对 通过产生细胞外DNA陷阱的肉芽肿形成和病原体控制 将研究细菌病毒因子的操作（AIM 1）。另外，我们将表征 MLN中STM持久性期间嗜酸性粒细胞的免疫调节效应子功能（AIM 2）。