A stress sensor IRE1α is required for bacterial exotoxin-induced inflammasome activation in tissue-resident macrophages
Ontology highlight
ABSTRACT: Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of a proinflammatory cytokine, interleukine-1β (IL-1β), in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. It, however, remains unclear how CTB or CT induces IL-1β production in the macrophages. Here we clarified roles of an endoplasmic reticulum (ER) stress sensor, IRE1α, in CT-induced IL-1β production from RPMs. In RPMs, CTB resided in the ER and induced ER stress responses, depending on a cell membrane ganglioside, GM1. Analysis with pharmacological inhibitors and gene-manipulated mice revealed that IRE1α was required for in CT- or CTB-induced IL-1β production from RPMs. This study first demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.
ORGANISM(S): Mus musculus
PROVIDER: GSE228915 | GEO | 2024/03/24
REPOSITORIES: GEO
ACCESS DATA