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Interleukin-33 signaling exacerbates experimental infectious colitis by enhancing gut permeability and inhibiting protective Th17 immunity
- Source :
- Mucosal Immunology, 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
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group US, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Immunology
Medizin
Infectious Colitis
T-Lymphocytes, Regulatory
Article
Permeability
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Immunity
medicine
Citrobacter rodentium
Immunology and Allergy
Animals
Lymphocyte Count
Colitis
Intestinal Mucosa
Pathogen
Citrobacter
biology
business.industry
Enterobacteriaceae Infections
500 Naturwissenschaften und Mathematik::570 Biowissenschaften
Biologie::570 Biowissenschaften
Biologie
medicine.disease
biology.organism_classification
Interleukin-33
cytokines
Interleukin 33
Disease Models, Animal
030104 developmental biology
intestinal infections
570 Life sciences
Th17 Cells
Disease Susceptibility
microbial pathogens
business
Biomarkers
030215 immunology
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19353456 and 19330219
- Volume :
- 14
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Mucosal Immunology
- Accession number :
- edsair.doi.dedup.....68dbdb99843faea00c26242e0621a45c