Wallet Pierre, Lagrange Brice, Henry Thomas
Centre International de Recherche en Infectiologie, Lyon, France.
Inserm U1111, CNRS UMR5308, Lyon, France.
Curr Top Microbiol Immunol. 2016;397:229-56. doi: 10.1007/978-3-319-41171-2_12.
Francisella tularensis is a facultative intracellular bacterium causing tularemia, a zoonotic disease. Francisella replicates in the macrophage cytosol and eventually triggers cytosolic immune responses. In murine macrophages, Francisella novicida and Francisella tularensis live vaccine strain lyse in the host cytosol and activate the cytosolic DNA receptor Aim2. Here, we review the mechanisms leading or contributing to Aim2 inflammasome activation, including the role of TLRs and of IFN signaling and the implication of the guanylate-binding proteins 2 and 5 in triggering cytosolic bacteriolysis. Furthermore, we present how this cytosolic Gram-negative bacterium escapes recognition by caspase-11 but can trigger a non-canonical caspase-8 inflammasome. In addition, we highlight the differences in inflammasome activation in murine and human cells with pyrin, NLRP3, and AIM2 involved in sensing Francisella in human phagocytes. From a bacterial prospective, we describe the hiding strategy of Francisella to escape recognition by innate sensors and to resist to bacteriolysis in the host cytosol. Finally, we discuss the inability of the inflammasome sensors to detect F. tularensis subspecies tularensis strains, making them highly pathogenic stealth microbes.
土拉弗朗西斯菌是一种兼性胞内细菌，可引起兔热病，这是一种人畜共患病。土拉弗朗西斯菌在巨噬细胞胞质溶胶中复制，并最终触发胞质免疫反应。在小鼠巨噬细胞中，新凶手弗朗西斯菌和土拉弗朗西斯菌活疫苗株在宿主胞质溶胶中裂解，并激活胞质DNA受体Aim2。在此，我们综述导致或促成Aim2炎性小体激活的机制，包括Toll样受体（TLRs）和干扰素信号传导的作用，以及鸟苷酸结合蛋白2和5在触发胞质细菌溶解中的作用。此外，我们介绍了这种胞质革兰氏阴性细菌如何逃避半胱天冬酶-11的识别，但能触发非经典半胱天冬酶-8炎性小体。另外，我们强调了在小鼠和人类细胞中炎性小体激活的差异，其中吡啉、NLRP3和AIM2参与人类吞噬细胞中土拉弗朗西斯菌的感知。从细菌的角度来看，我们描述了土拉弗朗西斯菌逃避先天传感器识别并抵抗宿主胞质溶胶中细菌溶解的隐藏策略。最后，我们讨论了炎性小体传感器无法检测土拉弗朗西斯菌土拉热亚种菌株，使其成为高致病性的隐形微生物。
