Cell Reports (Apr 2024)
A stress sensor, IRE1α, is required for bacterial-exotoxin-induced interleukin-1β production in tissue-resident macrophages
- Izumi Sasaki,
- Yuri Fukuda-Ohta,
- Chihiro Nakai,
- Naoko Wakaki-Nishiyama,
- Chizuyo Okamoto,
- Daisuke Okuzaki,
- Shuhei Morita,
- Shiori Kaji,
- Yuki Furuta,
- Hiroaki Hemmi,
- Takashi Kato,
- Asumi Yamamoto,
- Emi Tosuji,
- Shin-Ichiroh Saitoh,
- Takashi Tanaka,
- Katsuaki Hoshino,
- Shinji Fukuda,
- Kensuke Miyake,
- Etsushi Kuroda,
- Ken J. Ishii,
- Takao Iwawaki,
- Koichi Furukawa,
- Tsuneyasu Kaisho
Affiliations
- Izumi Sasaki
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Corresponding author
- Yuri Fukuda-Ohta
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Laboratory for Protein Conformation Diseases, RIKEN Center for Brain Science, Wako, Saitama 351-0198, Japan
- Chihiro Nakai
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Naoko Wakaki-Nishiyama
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Chizuyo Okamoto
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Daisuke Okuzaki
- Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
- Shuhei Morita
- First Department of Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Shiori Kaji
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Yuki Furuta
- Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama 641-8509, Japan
- Hiroaki Hemmi
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Laboratory of Immunology, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime 794-8555, Japan
- Takashi Kato
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Asumi Yamamoto
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Emi Tosuji
- Department of Dermatology, Wakayama Medical University, Wakayama 641-8509, Japan
- Shin-Ichiroh Saitoh
- Department of Intractable Disorders, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
- Takashi Tanaka
- Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa 230-0045, Japan
- Katsuaki Hoshino
- Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan
- Shinji Fukuda
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa 210-0821, Japan; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
- Kensuke Miyake
- Division of Innate Immunity, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
- Etsushi Kuroda
- Department of Immunology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan
- Ken J. Ishii
- Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
- Takao Iwawaki
- Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan
- Koichi Furukawa
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Aichi 487-8501, Japan
- Tsuneyasu Kaisho
- Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 4
p. 113981
Abstract
Summary: 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.
