<i>Listeria monocytogenes</i> is sensed by the NLRP3 and AIM2 inflammasome

TLDR

The inflammasome pathway regulates caspase‑1 activation, leading to IL‑1β maturation and pyroptosis, and is crucial for recognizing pathogens such as *Listeria monocytogenes*, though the specific inflammasome pathways activated during infection remain poorly defined. Our data show that *Listeria monocytogenes* activates both NLRP3 and AIM2 inflammasomes, with AIM2 predominating, and that loss of both sensors reduces pyroptosis and permits greater bacterial replication, confirming a key role for AIM2‑mediated DNA sensing in detecting intracellular Listeria.

Abstract

Abstract 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‐1β 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.