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Induction of the ISR by AB5 subtilase cytotoxin drives type-I IFN expression in pDCs via STING activation

ABSTRACT: We demonstrate that exposure to the Shiga AB5 subtilase cytotoxin (SubAB) induces the unfolded protein response (UPR) in human peripheral blood mononuclear cells, concomitant with a pro-inflammatory response across distinct cell subsets. Notably, SubAB selectively induces type-I interferon (IFN) expression in plasmacytoid dendritic cells, acting synergistically with Toll-like receptor 7 stimulation. The induction of type-I IFN in response to SubAB relies on stimulator of interferon genes (STING) activation, coupled with protein synthesis inhibition mediated by protein kinase R-like endoplasmic reticulum kinase and phosphorylation of the eukaryotic translation initiation factor 2 subunit-alpha. By impeding mRNA translation through the integrated stress response, SubAB precipitates the downregulation of the negative innate signaling feedback regulator Tax1-binding protein 1. This downregulation is necessary to unleash TANK-binding kinase 1 signaling associated with STING activation. These findings shed new light on how UPR-inducing conditions may regulate the immune system during infection or pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277164 | GEO | 2025/05/05

REPOSITORIES: GEO

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Induction of antiviral Interferon-Stimulated Genes (ISGs) by neuronal STING promotes the resolution of pain

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Induction of the ISR by AB5 subtilase cytotoxin drives type-I IFN expression in pDCs via STING activation

Project description:Induction of the ISR by AB5 subtilase cytotoxin drives type-I IFN expression in pDCs via STING activation

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