The Antimicrobial Response of Human Neutrophils to Opportunistic Pathogens

这个项目将研究人类中性粒细胞使用两种条件人类病原体，白色念珠菌和铜绿假单胞菌的抗菌素反应。虽然这些微生物通常是共生的，而不是致病的，但在已经患病或免疫受损的患者中，这两种微生物都可以导致对目前的抗菌疗法产生耐药性的危及生命的感染。中性粒细胞是对这些病原体的初始先天免疫反应的重要组成部分，因此是了解这些微生物如何被健康的免疫系统控制的关键。该项目将从人的血液中提取中性粒细胞，然后在体外将它们暴露于白色念珠菌和铜绿假单胞菌，使用细胞死亡分析、荧光显微镜、总蛋白质组学和磷酸蛋白质组学来测量对中性粒细胞和微生物的影响。这些结果将为中性粒细胞生物学提供更多的洞察力，并可能为未来的研究提供信息，以开发针对机会性病原体的新疗法。

This project will study the antimicrobial responses of human neutrophils using two opportunistic human pathogens, the fungus Candida albicans and the bacterium Pseudomonas aeruginosa. Although these microorganisms are usually commensal rather than pathogenic, in patients that are already sick or immunocompromised both organisms can cause life-threatening infections resistant to current antimicrobial therapies. Neutrophils are an essential component of the initial innate immune response to these pathogens, and so are key to understanding how these microbes are held in check by a healthy immune system. This project will extract neutrophils from human blood and then expose them in vitro to C. albicans and P. aeruginosa, measuring the effect on both neutrophil and microbe using cell-death assays, fluorescence microscopy, total proteomics and phospho-proteomics. These results will offer greater insight into neutrophil biology, and may inform future research to develop new treatments for opportunistic pathogens.