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IFNγ sensitizes macrophages to pathogen ligand killing via a unique caspase-8 and mitochondrial cell death pathway licensed by nitric oxide

ABSTRACT: Caspase-8 modulates TLR-induced gene transcription, which is only partially dependent on caspase-8 catalytic activity. Moreover, The slow kinetics of IFNγ and LPS-induced BMDM killing offers the possibility that transcriptional responses may contribute to cell death activation. We performed 3' mRNA-sequencing to examine whether caspase-8 might contribute, at least in part, to IFNγ and LPS-triggered macrophage death via its transcriptional role. We found that caspase-8-mediated transcriptional re-programming of BMDMs. Importantly, caspase-8 modulates expression of Bcl-2 family members and inducible nitric oxide synthase (iNOS) to promote activation of the mitochondrial apoptotic effectors, BAX and BAK.

ORGANISM(S): Mus musculus

PROVIDER: GSE161179 | GEO | 2021/12/15

REPOSITORIES: GEO

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IFNγ sensitizes macrophages to pathogen ligand killing via a unique caspase-8 and mitochondrial cell death pathway licensed by nitric oxide

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