RT Journal Article SR Electronic T1 Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against Francisella novicida JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 3662 OP 3668 DO 10.4049/jimmunol.1800788 VO 201 IS 12 A1 Zhu, Qifan A1 Zheng, Min A1 Balakrishnan, Arjun A1 Karki, Rajendra A1 Kanneganti, Thirumala-Devi YR 2018 UL http://www.jimmunol.org/content/201/12/3662.abstract AB The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to Francisella tularensis subspecies novicida infection, leading to maturation of IL-1β and IL-18 and pyroptosis. AIM2 is critical for host protection against F. novicida infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11. In this study, we report that GSDMD-deficient mice were susceptible to F. novicida infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in F. novicida–infected bone marrow–derived macrophages. Furthermore, caspase-1 activation was compromised in bone marrow–derived macrophages lacking GSDMD stimulated with other AIM2 inflammasome triggers, including poly(dA:dT) transfection and mouse CMV infection. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in promoting caspase-1 activation by AIM2 inflammasome.This article is featured in In This Issue, p.3477