1. A stress sensor, IRE1α, is required for bacterial-exotoxin-induced interleukin-1β production in tissue-resident macrophages.
- Author
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Sasaki I, Fukuda-Ohta Y, Nakai C, Wakaki-Nishiyama N, Okamoto C, Okuzaki D, Morita S, Kaji S, Furuta Y, Hemmi H, Kato T, Yamamoto A, Tosuji E, Saitoh SI, Tanaka T, Hoshino K, Fukuda S, Miyake K, Kuroda E, Ishii KJ, Iwawaki T, Furukawa K, and Kaisho T
- Subjects
- Animals, Mice, Inflammasomes metabolism, Mice, Inbred C57BL, Macrophages metabolism, Macrophages drug effects, Macrophages, Peritoneal metabolism, Macrophages, Peritoneal drug effects, Macrophages, Peritoneal immunology, Lipopolysaccharides pharmacology, Endoplasmic Reticulum metabolism, Interleukin-1beta metabolism, Endoribonucleases metabolism, Protein Serine-Threonine Kinases metabolism, Endoplasmic Reticulum Stress drug effects, Cholera Toxin pharmacology, Cholera Toxin metabolism
- 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 interleukin-1β (IL-1β), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1β production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1β production, indicating that IRE1α is required for CT- or CTB-induced IL-1β production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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