Although it is tempting to speculate that in rare cases of systemic C. difficile toxin dissemination, activation of the Pyrin inflammasome in myeloid cells might exert a detrimental role to the host by promoting excessive myeloid cell pyroptosis and inflammatory tissue damage, our results suggest that the Pyrin inflammasome is dispensable for host defense during self-limiting pseudomembranous colitis. Here, MEFV is linked to colitis.