Speir Mary, Vince James E, Naderer Thomas
Department of Biochemistry & Molecular Biology, Monash University, Clayton, 3800 Victoria, Australia.
Future Microbiol. 2014;9(1):107-18. doi: 10.2217/fmb.13.139.
The causative agent of Legionnaires' disease, Legionella pneumophila, resides within alveolar macrophages by exporting 295 bacterial virulence proteins (effectors) to modulate host cell processes. This leads to the formation of a unique vacuolar niche and the suppression of macrophage cell death pathways, which, in turn, promote bacterial survival and allow sufficient time for replication. However, once nutrients within the vacuole are depleted, Legionella must act to induce host cell death in order to facilitate bacterial egress and reinfect new cells. Intracellular Legionella also evade detection by the host cell's innate immune system, which seeks to destroy invading pathogens by activating inflammasome complexes, thereby promoting proinflammatory cytokine activation and pyroptotic cell death. Understanding how different forms of programmed cell death contribute to Legionella infectivity and are manipulated by Legionella effector proteins will be important for identifying novel antibacterial therapeutic targets.
军团病的病原体嗜肺军团菌，通过输出295种细菌毒力蛋白（效应蛋白）来调节宿主细胞过程，从而寄生于肺泡巨噬细胞内。这导致形成独特的液泡微环境，并抑制巨噬细胞的细胞死亡途径，进而促进细菌存活并为复制留出足够时间。然而，一旦液泡内的营养物质耗尽，嗜肺军团菌必须采取行动诱导宿主细胞死亡，以便促进细菌逸出并再次感染新细胞。细胞内的嗜肺军团菌还能逃避宿主细胞先天免疫系统的检测，先天免疫系统试图通过激活炎性小体复合物来破坏入侵的病原体，从而促进促炎细胞因子的激活和焦亡性细胞死亡。了解不同形式的程序性细胞死亡如何影响嗜肺军团菌的感染性以及如何被嗜肺军团菌效应蛋白操纵，对于确定新的抗菌治疗靶点至关重要。
