Role of eosinophils during bacterial infection

项目摘要 嗜酸性粒细胞的流入通常与过敏期间的II型反应相关。最近的报告显示 嗜酸性粒细胞具有重要的免疫调节作用，以及对抗蠕虫的关键抗菌作用， 病毒和一些细菌物种。然而，嗜酸性粒细胞如何有助于 消除细菌是研究不足，结果是完全不同的感染 病原体和急性与慢性感染。在本申请中，我们提出研究 在129 X1/Sv/J小鼠的肠系膜淋巴结（MLN）内持续沙门氏菌感染期间嗜酸性粒细胞。 我们未发表的数据显示，嗜酸性粒细胞，我们已经定位于含STm的肉芽肿，增加 在鼠伤寒沙门氏菌（STm）感染的前8周， 嗜酸性粒细胞化学引诱物CCL 11的增加。此外，STm感染小鼠中嗜酸性粒细胞的耗竭 使小鼠更容易受到感染。重要的是，嗜酸性粒细胞耗竭的小鼠的 与IgG 2对照相比，IFNγ产生细胞和IFNγ的组织水平较低，表明嗜酸性粒细胞 通过影响肉芽肿微环境使其向Th 1偏斜而有助于病原体控制。我们的中央 一种假说认为，感染组织中嗜酸性粒细胞的功能受微环境的调节， 作为肉芽肿，并在持续感染期间起到遏制病原体的作用。嗜酸性粒细胞对 肉芽肿形成和病原体控制通过生产细胞外DNA陷阱和可能 将研究细菌毒力因子的操纵（目的1）。此外，我们将描述 在MLN中STm持续期间嗜酸性粒细胞的免疫调节效应子功能（目的2）。

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 Our unpublished data show that eosinophils, which we have localized to STm-containing granulomas, increased significantly over the first 8 weeks of Salmonella enterica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