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

Pei Yun Tsai, Bingkun Zhang, Wei Qi He, Juan Min Zha, Matthew A. Odenwald, Gurminder Singh, Atsushi Tamura, Le Shen, Anne Sailer, Sunil Yeruva, Wei Ting Kuo, Yang Xin Fu, Sachiko Tsukita, Jerrold R. Turner

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)671-681.e4
JournalCell Host and Microbe
Volume21
Issue number6
DOIs
StatePublished - Jun 14 2017

Keywords

  • bacterial infection
  • colitis
  • diarrhea
  • enteric infection
  • innate defense
  • permeability
  • tight junction

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Tsai, P. Y., Zhang, B., He, W. Q., Zha, J. M., Odenwald, M. A., Singh, G., Tamura, A., Shen, L., Sailer, A., Yeruva, S., Kuo, W. T., Fu, Y. X., Tsukita, S., & Turner, J. R. (2017). IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance. Cell Host and Microbe, 21(6), 671-681.e4. https://doi.org/10.1016/j.chom.2017.05.009