Interaction Of Pathogenic Bacteria With Human Phagocytic

人类多形核白细胞（PMNs或中性粒细胞）是必不可少的先天免疫反应对抗入侵的微生物。与依赖于先前与特定细菌相互作用的获得性免疫反应相反，pmn杀死微生物的能力是即时的和非特异性的。由于pmn产生剧毒的杀微生物成分，因此控制感染诱导的炎症对于限制宿主组织破坏至关重要。鉴于pmn是大多数细菌感染的主要免疫细胞，这种调节尤为重要。我们研究的一个关键方面是研究PMNs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。因此，我们的研究目标之一是阐明人类pmn中促进感染解决的分子过程。为此，我们使用基因组学方法建立了宿主细胞-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。

Human polymorphonuclear leukocytes (PMNs or neutrophils) are essential to the innate immune response against invading microorganisms. In contrast to the acquired immune response, which is dependent on previous interaction with specific bacteria, the ability of PMNs to kill microorganisms is immediate and non-specific. Inasmuch as PMNs produce highly toxic microbicidal components, moderation of infection-induced inflammation is critical for limiting host tissue destruction. This moderation is especially important given that PMNs are the predominant immune cell in most bacterial infections. 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. Thus, one of our research objectives is to elucidate molecular processes in human PMNs that facilitate resolution of infection. To that end, we used genomics methodologies to establish a global model of host cell-pathogen interaction that provides fundamental insight into the resolution of infection in humans. A second focus of research in my laboratory investigates how bacterial pathogens such as Staphylococcus aureus and Streptococcus pyogenes (Group A Streptococcus or GAS) evade human innate host defense to cause disease. Although most bacteria are killed readily by PMNs, some human pathogens have evolved mechanisms to inhibit phagocytosis and death resulting from exposure to ROS and microbicidal products. For example, strains of S. aureus which produce Panton-Valentine leukocidin cause lethal necrotizing pneumonia in non-immunocomprimised individuals, the molecular basis for which is unknown. We hypothesize staphylococcal pathogenesis includes evasion of PMN killing and undetermined host-susceptibility factors. GAS successfully evades PMN phagocytosis and killing to cause human infections such as pharyngitis and necrotizing fasciitis (flesh-eating syndrome). To date, our studies include identification of genes and proteins used by GAS to evade destruction by human neutrophils, hence contributing to GAS virulence, survival and pathogenesis. These studies identified new potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections.