IRF2 deficiency disrupts pyroptosis, NK cell interferon-γ production and resistance to Francisella

ABSTRACT: IRF2 plays an indirect role in inflammasome activation by regulating Caspase-4 and Gasdermin D (GSDMD) levels. However, the in vivo relevance of this regulatory circuit is unknown. We generate IRF2KO mice and demonstrate that they are equally susceptible to Francisella novicida infection as GSDMDKO mice. Interestingly, the phenotypes of IRF2KO and GSDMDKO mice diverge with respect to IFN-γ. Specifically, IRF2KO mice exhibit a profound defect in IFN-γ production, which we attribute to an intrinsic role of IRF2 in regulating both the number and maturation of NK cells. IRF2KO NK cells fail to express the antibacterial effectors IL-18R and Granzyme A, thereby impairing bacterial clearance. IFN-γ therapy partially restores immune responses in IRF2KO mice and resistance to infection. These findi

SUBMITTER: Maxence Cornut 

PROVIDER: S-SCDT-10_1038-S44319-026-00698-4 | biostudies-other |

REPOSITORIES: biostudies-other