Interaction of pathogenic bacteria with human phagocytic leukocytes

致病菌与人类吞噬白细胞的相互作用

• 批准号: 8336155
• 负责人: Frank DeLeo
• 金额: $ 20.46万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336155
• 关键词: Apoptosis; Bacteria; Bacterial Infections; Cells; Disease; Host Defense; Human; Immune; Immune response; Infection; Inflammation; Invaded; Leukocytes; Modeling; Molecular; Phagocytosis; Phase; Play; Process; Research; Resolution; Role; Time; Tissues; insight; killings; microbicide; microorganism; neutrophil; pathogen; pathogen exposure; pathogenic bacteria

In 2011, we investigated the role played by human polymorphonuclear leukocytes (PMNs or neutrophils) in host defense against bacterial pathogens. Neutrophils are essential to the innate immune response against invading microorganisms. In contrast to the acquired immune response, which requires time to develop and is dependent on previous interaction with specific pathogens, the ability of PMNs to kill infectious microorganisms is immediate, non-specific, and not dependent on previous pathogen exposure. Inasmuch as PMNs produce toxic microbicidal components and are the predominant immune cell in most bacterial infections, moderation of infection-induced inflammation is critical for limiting host tissue destruction. Recent evidence suggests PMN apoptosis facilitates resolution of bacterial infections, an idea supported by the finding that pathogens alter neutrophil apoptosis to survive. A key aspect of our research investigates how PMNs ingest and kill bacteria, and elucidates post-phagocytosis sequelae such as apoptosis, processes crucial for the resolution phase of inflammation. These studies established a global model of host cell-pathogen interaction that provides fundamental insight into the resolution of infection in humans.

在2011年，我们研究了人类多形核白细胞（PMN或中性粒细胞）在宿主防御细菌病原体中的作用。 嗜中性粒细胞对于抵抗入侵微生物的先天免疫应答是必不可少的。与获得性免疫应答不同，获得性免疫应答需要时间来发展，并且依赖于先前与特定病原体的相互作用，中性粒细胞杀死感染性微生物的能力是立即的、非特异性的，并且不依赖于先前的病原体暴露。由于PMNs产生有毒的杀微生物成分，并且是大多数细菌感染中的主要免疫细胞，因此感染诱导的炎症的缓和对于限制宿主组织破坏至关重要。最近的证据表明，中性粒细胞凋亡促进细菌感染的解决，病原体改变中性粒细胞凋亡存活的发现支持了这一观点。我们研究的一个关键方面是研究中性粒细胞如何摄取和杀死细菌，并阐明吞噬后的后遗症，如细胞凋亡，这是炎症消退阶段的关键过程。 这些研究建立了宿主细胞-病原体相互作用的全球模型，为人类感染的解决提供了基本的见解。