Fusobacterium nucleatum infection activates the noncanonical inflammasome and exacerbates inflammatory response in DSS‐induced colitis

Author:

Boonyaleka Kotchakorn1ORCID,Okano Tokuju1ORCID,Iida Tamako1,Leewananthawet Anongwee23,Sasai Miwa4,Yamamoto Masahiro4,Ashida Hiroshi1,Suzuki Toshihiko1ORCID

Affiliation:

1. Department of Bacterial pathogenesis, Infection, and Host Response, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan

2. Department of Restorative Dentistry and Periodontology, Faculty of Dentistry Chiang Mai University Chiang Mai Thailand

3. Department of Restorative Dentistry and Periodontology, Specialized Dental Center of Faculty of Dentistry Chiang Mai University Chiang Mai Thailand

4. Department of Immunoparasitology, Research Institute for Microbial Diseases Osaka University Osaka Japan

Abstract

AbstractCaspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular contents. Fusobacterium nucleatum is a periodontal pathogen frequently detected in human cancer and inflammatory bowel diseases. Studies have reported that F. nucleatum infection leads to NLRP3 activation and pyroptosis, but the precise activation process and disease association remain poorly understood. This study demonstrated that F. nucleatum infection exacerbates acute colitis in mice and activates pyroptosis through caspase‐11‐mediated gasdermin D cleavage in macrophages. Furthermore, F. nucleatum infection in colitis mice induces the enhancement of IL‐1⍺ secretion from the colon, affecting weight loss and severe disease activities. Neutralization of IL‐1⍺ protects F. nucleatum infected mice from severe colitis. Therefore, F. nucleatum infection facilitates inflammation in acute colitis with IL‐1⍺ from colon tissue by activating noncanonical inflammasome through gasdermin D cleavage.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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