Zhu, QifanMan, Si MingKarki, RajendraMalireddi, R.K. SubbaraoKanneganti, Thirumala-Devi2019-04-102019-04-102211-1247http://hdl.handle.net/1885/159454Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice. Mice lacking both AIM2 and IFNAR2 were protected against the infection. The detrimental effects of type I IFN signaling were due to its ability to induce activation of apoptotic caspases and cell death. These results demonstrate the contrasting effects of type I IFN signaling and AIM2 during F. novicida infection in vivo and indicate a dominant role for type I IFNs in mediating detrimental responses despite the protective AIM2 inflammasome responses.application/pdfen-AUThis is an open access article under the CC BY-NC-ND licenseAuthor/s retain copyrighthttp://creativecommons.org/licenses/by-nc-nd/4.0/201810.1016/j.celrep.2018.02.0962019-03-12