| First Author | Zhu Q | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 12 | Pages | 3662-3668 |
| PubMed ID | 30404813 | Mgi Jnum | J:268263 |
| Mgi Id | MGI:6269224 | Doi | 10.4049/jimmunol.1800788 |
| Citation | Zhu Q, et al. (2018) Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against Francisella novicida. J Immunol 201(12):3662-3668 |
| abstractText | 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-1beta 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. |
