Interaction of pathogenic bacteria with human phagocytic leukocytes

在2013财年，我们研究了人多形核白细胞(PMN或中性粒细胞)在宿主防御细菌病原体中所起的作用。中性粒细胞是抵御入侵微生物的先天免疫反应的关键。获得性免疫反应需要时间才能形成，并依赖于先前与特定病原体的相互作用，而PMN杀死感染微生物的能力是直接的、非特异性的，并且不依赖于先前的病原体暴露。由于中性粒细胞产生有毒的杀微生物活性成分，并且是大多数细菌感染的主要免疫细胞，控制感染诱导的炎症对于限制宿主组织的破坏至关重要。最近的证据表明，PMN的凋亡有助于细菌感染的解决，这一观点得到了病原体改变中性粒细胞凋亡以生存的发现的支持。我们研究的一个关键方面是调查PMN如何吞噬和杀死细菌，并阐明吞噬后的后遗症，如细胞凋亡，这是炎症消退阶段至关重要的过程。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。

In FY2013, 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.