Pathogens are detected by innate immune receptors that, upon activation, orchestrate an appropriate immune response. Recent studies revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella abortus
infection. However, no report has elucidated the role of
inflammasome receptors in Brucella recognition. Therefore, we decided to investigate the function of NLRC4, NLRP3, and AIM2 in sensing Brucella. In this study, we showed that NLRC4 is not required to induce caspase-1 activation and further secretion of IL-1β by B. abortus in macrophages. In contrast, we determined that AIM2, which senses Brucella
DNA, and NLRP3 are partially required for caspase-1 activation and IL-1β secretion. Additionally, mitochondrial
reactive oxygen species induced by Brucella were implicated in IL-1β production. Furthermore, AIM2, NLRP3, ASC, and caspase-1 knockout mice were more susceptible to B. abortus
infection than were wild-type animals, suggesting that multiple ASC-dependent
inflammasomes contribute to host protection against
infection. This protective effect is due to the inflammatory response caused by IL-1β and
IL-18 rather than pyroptosis, because we observed augmented bacterial burden in IL-1R and
IL-18 knockout mice. Finally, we determined that bacterial
type IV secretion system VirB and live, but not heat-killed, Brucella are required for full
inflammasome activation in macrophages during
infection. Taken together, our results indicate that Brucella is sensed by ASC
inflammasomes that collectively orchestrate a robust caspase-1 activation and proinflammatory response.