Mycobacterium tuberculosis does not inhibit NLRP1 and pyrin inflammasomes in human macrophages.

Mycobacterium tuberculosis (Mtb) has been known to evade host innate immunity by manipulating macrophage function. Interleukin-1β (IL-1β) is a cytokine secreted by macrophages as a consequence of inflammasome activation. Mtb can inhibit activation of the NLRP3 and AIM2 inflammasomes and subsequent pyroptosis. The capacity of Mtb to manipulate other types of inflammasomes is unknown. In this study, we investigated whether Mtb or the nontuberculous mycobacteria Mycobacterium kansasii (Mkan) and Mycobacterium smegmatis (Msmeg) can inhibit the NLRP1 or pyrin inflammasomes. We show that none of the mycobacteria consistently inhibit the NLRP1 inflammasome after it is activated by priming with lipopolysaccharide (LPS) and treatment with 1G244 in human macrophages. Similarly, neither Mtb nor the NTMs inhibit the pyrin inflammasome after it is activated by priming with LPS and treating with TcdB toxin from Clostridium difficile in human macrophages. In murine macrophages, Mkan shows inhibition only at 3 h post-infection, and Msmeg, only at 24 h post-infection, whereas no inhibition was observed at any time point for Mtb. In conclusion, our main findings are that Mtb is unable to inhibit the NLRP1 and the pyrin inflammasomes in human macrophages.IMPORTANCEThe research focuses on the interaction of mycobacteria with BMDMs and hMDMs regarding NLRP1 and pyrin inflammasome inhibition. We think that these results point to insights into the pathways of pathogen recognition in macrophages, which may have broader implications for host defense. These results are technically sound and provide new information to the field by showing that various mycobacteria do not inhibit the NLRP1 and Pyrin inflammasomes, at least under our specific experimental settings. Important limitations to the study are its narrow scope and limited mechanistic depth.