Institute for Clinical Chemistry and Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany.
Eur J Immunol. 2010 Jun;40(6):1545-51. doi: 10.1002/eji.201040425.
The inflammasome pathway functions to regulate caspase-1 activation in response to a broad range of stimuli. Caspase-1 activation is required for the maturation of the pivotal pro-inflammatory cytokines of the pro-IL-1beta family. In addition, caspase-1 activation leads to a certain type of cell death known as pyroptosis. Activation of the inflammasome has been shown to play a critical role in the recognition and containment of various microbial pathogens, including the intracellularly replicating Listeria monocytogenes; however, the inflammasome pathways activated during L. monocytogenes infection are only poorly defined. Here, we demonstrate that L. monocytogenes activates both the NLRP3 and the AIM2 inflammasome, with a predominant involvement of the AIM2 inflammasome. In addition, L. monocytogenes-triggered cell death was diminished in the absence of both AIM2 and NLRP3, and is concomitant with increased intracellular replication of L. monocytogenes. Altogether, these data establish a role for DNA sensing through the AIM2 inflammasome in the detection of intracellularly replicating bacteria.
炎症小体途径的功能是调节半胱天冬酶-1 的激活，以响应广泛的刺激。半胱天冬酶-1 的激活是前白细胞介素-1β家族中关键促炎细胞因子成熟所必需的。此外，半胱天冬酶-1 的激活导致一种称为细胞焦亡的特定类型的细胞死亡。已经表明，炎症小体的激活在识别和控制各种微生物病原体方面起着关键作用，包括细胞内复制的李斯特菌；然而，李斯特菌感染期间激活的炎症小体途径还知之甚少。在这里，我们证明李斯特菌激活了 NLRP3 和 AIM2 炎症小体，其中 AIM2 炎症小体的参与占主导地位。此外，在缺乏 AIM2 和 NLRP3 的情况下，李斯特菌触发的细胞死亡减少，并且伴随着李斯特菌的细胞内复制增加。总之，这些数据确立了通过 AIM2 炎症小体进行 DNA 感应在检测细胞内复制细菌中的作用。
