NK cell IL-10 production during bacterial infections

细菌感染期间 NK 细胞产生 IL-10

基本信息

批准号：
9893333
负责人：
Laurel L Lenz
金额：
$ 9.21万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-10 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9893333
关键词：
Address Affect Bacterial Infections Binding CD8B1 gene Cell secretion Cells Colitis Data Dendritic Cells Development Disease Factor X Genetic Transcription Health Host resistance Human Immunity Immunization Infection Inflammatory Innate Immune Response Interferons Interleukin-10 Interleukin-18 Interleukins Licensing Life Link Listeria monocytogenes Lung Malignant Neoplasms Maps Messenger RNA Modeling Mucous Membrane Mus Mycobacterium tuberculosis Myeloid Cell Activation NK Cell Activation Natural Killer Cells Pneumococcal Infections Predisposition Production Proteins Recombinant Proteins Recombinants Resistance Signal Transduction Source Streptococcus pneumoniae Surface Systemic disease Systemic infection TIS11 protein Testing Transcript Virulence Virulence Factors Work commensal microbes cytokine experimental study hexachlorocyclohexane x-factor human disease improved mouse model novel therapeutic intervention pathogen pathogenic bacteria pathogenic microbe prevent response tumor

项目摘要

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.

项目概要粘膜屏障和先天免疫反应保护我们免受许多非致病性的侵入性感染然而，某些细菌病原体已经进化出穿过粘膜屏障的策略。我们的研究揭示了由此产生的严重的、危及生命的系统性感染的薄弱环节。这些病原体在其建立过程中利用了我们的先天免疫反应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 在病原体单核细胞增生李斯特氏菌全身感染期间产生 IL-10 是许多细胞因子。此前人们并没有认识到致病菌在严重感染过程中的利用。 NK 细胞是“亲细菌”IL-10 产生的主要来源，我们进一步发现分泌性 L. 单核细胞增多性细菌毒力蛋白 p60 通过刺激树突促进 NK 细胞 IL-10 的产生我们的研究解决了这些细胞（DC）产生 IL-18 和其他必需因子的机制。我们还研究了 NK 细胞 IL-10 对 NK 细胞激活产生 IL-10 的影响。这些病原体穿过不同粘膜屏障形成全身性疾病的能力。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 产生的策略改善人类健康。