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Goblet Cell Derived RELM-β Recruits CD4 T Cells during Infectious Colitis to Promote Protective Intestinal Epithelial Cell Proliferation


Food and water-borne bacterial pathogens such as enterohemorrhagic Escherichia coli (EHEC) target the epithelial cells that line the inner surface of their host’s intestines, causing inflammation and diarrhea. While professional immune cells including T lymphocytes are well known for promoting host defense, we hypothesized that as the cells in closest contact with these bacterial pathogens, intestinal epithelial cells also play an active and essential role in protecting the host during infection. Infecting mice with Citrobacter rodentium, a mouse specific relative of EHEC, we noted a dramatic upregulation in the expression and secretion of the mediator RELM-β by a subset of epithelial cells called goblet cells. Compared to wildtype mice, mice lacking RELM-β showed less epithelial cell proliferation and suffered significantly more intestinal damage during infection. Rather than directly causing epithelial cell proliferation, we found RELM-β instead recruited T lymphocytes to the infected intestine. Upon reaching the intestine, the T lymphocytes produced the cytokine interleukin-22, which directly increased epithelial cell proliferation. Taken together, these findings indicate that epithelial/goblet cells play a critical role in orchestrating the host response to an intestinal pathogen, by recruiting T lymphocytes and by promoting epithelial proliferation to limit the intestinal damage suffered during infection.


Vyšlo v časopise: Goblet Cell Derived RELM-β Recruits CD4 T Cells during Infectious Colitis to Promote Protective Intestinal Epithelial Cell Proliferation. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005108
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005108

Souhrn

Food and water-borne bacterial pathogens such as enterohemorrhagic Escherichia coli (EHEC) target the epithelial cells that line the inner surface of their host’s intestines, causing inflammation and diarrhea. While professional immune cells including T lymphocytes are well known for promoting host defense, we hypothesized that as the cells in closest contact with these bacterial pathogens, intestinal epithelial cells also play an active and essential role in protecting the host during infection. Infecting mice with Citrobacter rodentium, a mouse specific relative of EHEC, we noted a dramatic upregulation in the expression and secretion of the mediator RELM-β by a subset of epithelial cells called goblet cells. Compared to wildtype mice, mice lacking RELM-β showed less epithelial cell proliferation and suffered significantly more intestinal damage during infection. Rather than directly causing epithelial cell proliferation, we found RELM-β instead recruited T lymphocytes to the infected intestine. Upon reaching the intestine, the T lymphocytes produced the cytokine interleukin-22, which directly increased epithelial cell proliferation. Taken together, these findings indicate that epithelial/goblet cells play a critical role in orchestrating the host response to an intestinal pathogen, by recruiting T lymphocytes and by promoting epithelial proliferation to limit the intestinal damage suffered during infection.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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