Palmieri, Vittoria; Ebel, Jana-Fabienne; Ngo Thi Phuong, Nhi; Klopfleisch, Robert; Vu, Vivian Pham; Adamczyk, Alexandra; Zöller, Julia; Riedel, Christian; Buer, Jan; Krebs, Philippe; Hansen, Wiebke; Pastille, Eva; Westendorf, Astrid M. (2021). Interleukin-33 signaling exacerbates experimental infectious colitis by enhancing gut permeability and inhibiting protective Th17 immunity. Mucosal immunology, 14(4), pp. 923-936. Springer Nature 10.1038/s41385-021-00386-7
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A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium. We observed that deficiency of the IL-33 signaling pathway attenuates bacterial-induced colitis. Conversely, boosting this pathway strongly aggravates the inflammatory response and makes the mice prone to systemic infection. Mechanistically, IL-33 mediates its detrimental effect by enhancing gut permeability and by limiting the induction of protective T helper 17 cells at the site of infection, thus impairing host defense mechanisms against the enteric pathogen. Importantly, IL-33-treated infected mice supplemented with IL-17A are able to resist the otherwise strong systemic spreading of the pathogen. These findings reveal a novel IL-33/IL-17A crosstalk that controls the pathogenesis of Citrobacter rodentium-driven infectious colitis. Manipulating the dynamics of cytokines may offer new therapeutic strategies to treat specific intestinal infections.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Vu, Vivian Pham, Krebs, Philippe |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
1935-3456 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Philippe Krebs |
Date Deposited: |
11 Mar 2021 09:04 |
Last Modified: |
05 Dec 2022 15:48 |
Publisher DOI: |
10.1038/s41385-021-00386-7 |
PubMed ID: |
33654214 |
BORIS DOI: |
10.48350/153359 |
URI: |
https://boris.unibe.ch/id/eprint/153359 |