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Haemolysin Ahh1 secreted from Aeromonas dhakensis activates the NLRP3 inflammasome in macrophages and mediates severe soft tissue infection.
Su, Yu-Cheng; Wang, Ching-Chun; Chen, Yi-Wei; Wang, Sin-Tian; Shu, Cing-Ying; Tsai, Pei-Jane; Ko, Wen-Chien; Chen, Chang-Shi; Chen, Po-Lin.
Afiliación
  • Su YC; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Wang CC; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Chen YW; Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90024, United States.
  • Wang ST; Department of Medical Laboratory Science and Biotechnology College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Shu CY; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Tsai PJ; Department of Medical Laboratory Science and Biotechnology College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Ko WC; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Chen CS; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • Chen PL; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. Electronic address: cplin@mail.nc
Int Immunopharmacol ; 128: 111478, 2024 Feb 15.
Article en En | MEDLINE | ID: mdl-38183913
ABSTRACT
Severe soft tissue infections caused by Aeromonas dhakensis, such as necrotizing fasciitis or cellulitis, are prevalent in southern Taiwan and around the world. However, the mechanism by which A. dhakensis causes tissue damage remains unclear. Here, we found that the haemolysin Ahh1, which is the major virulence factor of A. dhakensis, causes cellular damage and activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome signalling pathway. Deletion of ahh1 significantly downregulated caspase-1, the proinflammatory cytokine interleukin 1ß (IL-1ß) and gasdermin D (GSDMD) and further decreased the damage caused by A. dhakensis in THP-1 cells. In addition, we found that knockdown of the NLRP3 inflammasome confers resistance to A. dhakensis infection in both THP-1 NLRP3-/- cells and C57BL/6 NLRP3-/- mice. In addition, we demonstrated that severe soft-tissue infections treated with antibiotics combined with a neutralizing antibody targeting IL-1ß significantly increased the survival rate and alleviated the degree of tissue damage in model mice compared control mice. These findings show that antibiotics combined with therapies targeting IL-1ß are potential strategies to treat severe tissue infections caused by toxin-producing bacteria.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Bacterias Gramnegativas / Infecciones de los Tejidos Blandos / Aeromonas / Inflamasomas / Proteínas Hemolisinas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Bacterias Gramnegativas / Infecciones de los Tejidos Blandos / Aeromonas / Inflamasomas / Proteínas Hemolisinas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos