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IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance.

Cell host & microbe | Jun 14, 2017

Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na+ channel formed by claudin-2. Relative to wild-type, claudin-2-deficient mice experienced severe disease, including increased mucosal colonization by C. rodentium, prolonged pathogen shedding, exaggerated cytokine responses, and greater tissue injury. Conversely, transgenic claudin-2 overexpression reduced disease severity. Chemically induced osmotic diarrhea reduced colitis severity and C. rodentium burden in claudin-2-deficient, but not transgenic, mice, demonstrating that claudin-2-mediated protection is the result of enhanced water efflux. Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.

Pubmed ID: 28618266 RIS Download

Mesh terms: Animals | Cell Membrane Permeability | Citrobacter rodentium | Claudin-2 | Colitis | Cytokines | Diarrhea | Disease Models, Animal | Enterobacteriaceae Infections | Epithelium | Immunity, Innate | Interleukins | Intestinal Mucosa | Intestines | Mice | Mice, Inbred C57BL | Sodium | Tight Junctions | Up-Regulation | Water

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: R24 DK099803
  • Agency: NICHD NIH HHS, Id: T32 HD007009
  • Agency: NIDDK NIH HHS, Id: K01 DK092381
  • Agency: NIDDK NIH HHS, Id: R01 DK061931
  • Agency: NIDDK NIH HHS, Id: F32 DK009180
  • Agency: NIDDK NIH HHS, Id: P30 DK034854
  • Agency: NIDDK NIH HHS, Id: F30 DK103511
  • Agency: NIDDK NIH HHS, Id: R01 DK068271
  • Agency: NCRR NIH HHS, Id: S10 RR025643

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