NK cell IL-10 production during bacterial infections

项目摘要 粘液屏障和先天免疫反应保护我们免受许多非致病性的侵袭性感染。 细菌然而，某些细菌病原体已经进化出了穿过粘膜屏障的策略， 从而造成严重的、危及生命的全身性感染。我们的研究揭示了 我们假设的先天性免疫反应是由这些病原体在建立 全身性疾病。这些最近的研究暗示自然杀伤（NK）细胞是白细胞介素（IL）的主要来源。 10在病原体单核细胞增生李斯特菌的全身感染期间的产生。IL-10是一种细胞因子， 病原菌在严重感染的建立过程中发挥作用。以前没有认识到， NK细胞是“亲细菌”IL-10产生的主要来源。我们进一步发现，一个分泌的L。 单核细胞增多症细菌毒力蛋白p60通过刺激树突状细胞促进NK细胞IL-10的产生 细胞（DC）产生IL-18和其他必需因子。我们的研究在这里解决机制， 因子协调NK细胞活化以产生IL-10。我们还研究了NK细胞IL-10对 这些病原体能够穿过不同的粘膜屏障以建立全身性疾病。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.