Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Beech Hill Road, Sheffield S10 2TN, UK.
Florey Institute, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.
Int J Mol Sci. 2019 Nov 7;20(22):5561. doi: 10.3390/ijms20225561.
Neutrophils are key to host defence, and impaired neutrophil function predisposes to infection with an array of pathogens, with a common and sometimes life-threatening problem in this setting. Both infiltrating immune cells and replicating bacteria consume oxygen, contributing to the profound tissue hypoxia that characterises sites of infection. Hypoxia in turn has a dramatic effect on both neutrophil bactericidal function and the properties of , including the production of virulence factors. Hypoxia thereby shapes the host-pathogen interaction and the progression of infection, for example promoting intracellular bacterial persistence, enabling local tissue destruction with the formation of an encaging abscess capsule, and facilitating the establishment and propagation of bacterial biofilms which block the access of host immune cells. Elucidating the molecular mechanisms underlying host-pathogen interactions in the setting of hypoxia will enable better understanding of persistent and recalcitrant infections due to and may uncover novel therapeutic targets and strategies.
中性粒细胞是宿主防御的关键，而中性粒细胞功能受损会使机体容易感染一系列病原体，在这种情况下，常常会出现一种常见且有时危及生命的问题。浸润的免疫细胞和复制的细菌都会消耗氧气，导致感染部位的组织严重缺氧。缺氧反过来又对中性粒细胞的杀菌功能和特性产生巨大影响，包括毒力因子的产生。因此，缺氧会影响宿主-病原体相互作用和感染的进展，例如促进细胞内细菌持续存在，使局部组织破坏并形成包裹脓肿囊，以及促进细菌生物膜的建立和传播，从而阻止宿主免疫细胞的进入。阐明缺氧环境下宿主-病原体相互作用的分子机制将有助于更好地理解由于 引起的持续和难治性感染，并可能揭示新的治疗靶点和策略。
