Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2025

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

Induction de l'ISR par la cytotoxine AB5 subtilase induit l'expression de type-I IFN dans les pDCs via STING

Stéphane Rocchi
Yinming Liang

Résumé

We demonstrate that exposure to the AB5 subtilase cytotoxin (SubAB) induces the unfolded protein response (UPR) in human peripheral blood mononuclear cells, concomitant with a proinflammatory 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 (PERK) 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 light on how UPR-inducing conditions may regulate the immune system during infection or pathogenesis.

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hal-05348432 , version 1 (05-11-2025)

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Daniela Barros, Beatriz H Ferreira, Paulina Garcia-Gonzalez, Francesco Carbone, Marine Luka, et al.. Induction of the ISR by AB5 subtilase cytotoxin drives type-I IFN expression in pDCs via STING activation. Proceedings of the National Academy of Sciences of the United States of America, 2025, 122 (21), pp.e2421258122. ⟨10.1073/pnas.2421258122⟩. ⟨hal-05348432⟩
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