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IL-22-dependent responses and their role during Citrobacter rodentium infection.
Melchior, Karine; Gerner, Romana R; Hossain, Suzana; Nuccio, Sean-Paul; Moreira, Cristiano Gallina; Raffatellu, Manuela.
Afiliação
  • Melchior K; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
  • Gerner RR; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
  • Hossain S; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
  • Nuccio S-P; School of Life Sciences, ZIEL - Institute for Food and Health, Freising-Weihenstephan, Technical University of Munich, Munich, Germany.
  • Moreira CG; Department of Internal Medicine III, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.
  • Raffatellu M; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
Infect Immun ; 92(5): e0009924, 2024 May 07.
Article em En | MEDLINE | ID: mdl-38557196
ABSTRACT
The mouse pathogen Citrobacter rodentium is utilized as a model organism for studying infections caused by the human pathogens enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and to elucidate mechanisms of mucosal immunity. In response to C. rodentium infection, innate lymphoid cells and T cells secrete interleukin (IL)-22, a cytokine that promotes mucosal barrier function. IL-22 plays a pivotal role in enabling mice to survive and recover from C. rodentium infection, although the exact mechanisms involved remain incompletely understood. Here, we investigated whether particular components of the host response downstream of IL-22 contribute to the cytokine's protective effects during C. rodentium infection. In line with previous research, mice lacking the IL-22 gene (Il22-/- mice) were highly susceptible to C. rodentium infection. To elucidate the role of specific antimicrobial proteins modulated by IL-22, we infected the following knockout mice S100A9-/- (calprotectin), Lcn2-/- (lipocalin-2), Reg3b-/- (Reg3ß), Reg3g-/- (Reg3γ), and C3-/- (C3). All knockout mice tested displayed a considerable level of resistance to C. rodentium infection, and none phenocopied the lethality observed in Il22-/- mice. By investigating another arm of the IL-22 response, we observed that C. rodentium-infected Il22-/- mice exhibited an overall decrease in gene expression related to intestinal barrier integrity as well as significantly elevated colonic inflammation, gut permeability, and pathogen levels in the spleen. Taken together, these results indicate that host resistance to lethal C. rodentium infection may depend on multiple antimicrobial responses acting in concert, or that other IL-22-regulated processes, such as tissue repair and maintenance of epithelial integrity, play crucial roles in host defense to attaching and effacing pathogens.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citrobacter rodentium / Infecções por Enterobacteriaceae / Interleucina 22 Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citrobacter rodentium / Infecções por Enterobacteriaceae / Interleucina 22 Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos