Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against .

J Immunol 2018 12 7;201(12):3662-3668. Epub 2018 Nov 7.

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and

The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to subspecies infection, leading to maturation of IL-1β and IL-18 and pyroptosis. AIM2 is critical for host protection against 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 infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in -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.

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http://dx.doi.org/10.4049/jimmunol.1800788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317867PMC
December 2018

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