Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Future Microbiol. 2018 Jan;13(1):119-134. doi: 10.2217/fmb-2017-0142. Epub 2017 Dec 11.
Group A Streptococcus (GAS) is a leading human bacterial pathogen with diverse clinical manifestations. Macrophages constitute a critical first line of host defense against GAS infection, using numerous surface and intracellular receptors such as Toll-like receptors and inflammasomes for pathogen recognition and activation of inflammatory signaling pathways. Depending on the intensity of the GAS infection, activation of these signaling cascades may provide a beneficial early alarm for effective immune clearance, or conversely, may cause hyperinflammation and tissue injury during severe invasive infection. Although traditionally considered an extracellular pathogen, GAS can invade and replicate within macrophages using specific molecular mechanisms to resist phagolysosomal and xenophagic killing. Unraveling GAS-macrophage encounters may reveal new treatment options for this leading agent of infection-associated mortality. [Formula: see text].
A 组链球菌(GAS)是一种具有多种临床表现的主要人类细菌病原体。巨噬细胞是宿主抵御 GAS 感染的第一道重要防线,它们利用多种表面和细胞内受体,如 Toll 样受体和炎性小体,来识别病原体并激活炎症信号通路。根据 GAS 感染的强度,这些信号级联的激活可能为有效的免疫清除提供有益的早期警报,或者在严重侵袭性感染时导致过度炎症和组织损伤。尽管传统上被认为是一种细胞外病原体,但 GAS 可以利用特定的分子机制在巨噬细胞内入侵和复制,以抵抗吞噬溶酶体和异噬体的杀伤。揭示 GAS-巨噬细胞的相互作用可能为这种感染相关死亡的主要病原体提供新的治疗选择。