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Infect. Immun. doi:10.1128/IAI.00093-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen

Division of Gastroenterology, BC's Children's Hospital, Michael Smith Laboratories, Department of Department of Cellular and Physiological Sciences, Division of Anatomy and Cell Biology, University of British Columbia, Vancouver, British Columbia, Canada

^* To whom correspondence should be addressed. Email: bvallance{at}cw.bc.ca.

	Abstract

The attaching/effacing (A/E) bacterial pathogens Enteropathogenic and Enterohemorrhagic Escherichia coli, and the related mouse pathogen Citrobacter rodentium, colonize their host's intestines by infecting the apical surfaces of enterocytes, subverting their function, and they ultimately cause diarrhea. Surprisingly, little is known about their interactions with goblet cells, which are specialized epithelial cells that secrete the protective molecules Muc2 and Tff3 into the intestinal lumen. C. rodentium infection leads to dramatic goblet cell depletion within the infected colon; yet it is unclear whether C. rodentium infect goblet cells, or if this pathology is pathogen- or host-mediated. As determined by immunostaining and PCR, both goblet cell numbers, and expression of genes encoding Muc2 and Tff3 were significantly reduced by day 10 post infection. While electron microscopy and immunostaining revealed C. rodentium directly infected a fraction of colonic goblet cells, C. rodentium localization did not correlate with goblet cell depletion. To assess the role of the host immune system in these changes, Rag1 KO (T & B cell deficient) mice were infected with C. rodentium. Rag1 KO mice did not exhibit the reduction in goblet cell numbers or in mediator (Muc2, Tff3) expression observed in infected immunocompetent mice. However, reconstitution of Rag1 KO mice with T & B lymphocytes from C57BL/6 mice restored the goblet cell depletion phenotype during C. rodentium infection. In conclusion, these studies demonstrate that while colonic goblet cells can be subject to direct infection and potential subversion by A/E pathogens in vivo, it is the host immune system that primarily modulates the function of these cells during infection.