NK cell IL-10 production during bacterial infections

项目摘要 粘膜屏障和先天免疫反应保护我们免受许多非致病性疾病的侵袭性感染 细菌。然而，某些细菌病原体已经进化出跨越粘膜屏障和 从而造成严重的、危及生命的系统性感染。我们的研究揭示了一个薄弱的环节 我们假设的先天免疫反应被这些病原体在其建立过程中利用 系统性疾病。这些最近的研究表明，自然杀伤(NK)细胞是白细胞介素(IL)的主要来源。 10单核细胞增多性李斯特菌在全身感染期间产生。IL-10是一种细胞因子 病原菌在建立严重感染的过程中被利用。以前人们并没有意识到 NK细胞是“亲细菌”产生IL-10的主要来源。我们进一步发现，一种分泌型L. 单核细胞增多性细菌毒力蛋白p60通过刺激树突状细胞促进NK细胞IL-10的产生 树突状细胞(DC)产生IL-18和其他必需因子。我们在这里的研究解决了这些问题的机制 这些因子协调NK细胞的激活以产生IL-10。我们还研究了NK细胞IL-10对小鼠外周血中IL-10的影响。 这些病原体跨越不同的粘膜屏障建立系统性疾病的能力。机械论 通过这些研究获得的信息可能揭示促进或抑制NK细胞IL-10产生的策略 以改善人类健康。

Project Summary Mucosal barriers and innate immune responses protect us from invasive infection by many non-pathogenic bacteria. However, certain bacterial pathogens have evolved strategies to cross mucosal barriers and consequently establish severe, life-threatening systemic infections. Our studies have revealed a weak link in the innate immune response that we hypothesize is exploited by these pathogens during their establishment of systemic disease. These recent studies implicate natural killer (NK) cells as a major source of interleukin (IL)- 10 production during systemic infection by the pathogen Listeria monocytogenes. IL-10 is a cytokine that many pathogenic bacteria exploit during the establishment of severe infection. It was not previously appreciated that NK cells are the major source of “pro-bacterial” IL-10 production. We further found that a secreted L. monocytogenes bacterial virulence protein, p60, promotes NK cell IL-10 production by stimulating dendritic cells (DC) to produce IL-18 and other essential factors. Our studies here address mechanisms by which these factors coordinate NK cell activation to produce IL-10. We also investigate the impact of NK cell IL-10 on the ability of these pathogens to cross different mucosal barriers to establish systemic disease. The mechanistic information obtained through these studies may reveal strategies to promote or inhibit NK cell IL-10 production to improve human health.