This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00093-07v1 76/2/796    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Bergstrom, K. S. B. Articles by Vallance, B. A. PubMed PubMed Citation Articles by Bergstrom, K. S. B. Articles by Vallance, B. A.

Modulation of Intestinal Goblet Cell Function during Infection by an Attaching and Effacing Bacterial Pathogen

Kirk S. B. Bergstrom,^1, Julian A. Guttman,^2, Mohammad Rumi,¹ Caixia Ma,¹ Saied Bouzari,¹ Mohammed A. Khan,¹ Deanna L. Gibson,¹ A. Wayne Vogl,³ and Bruce A. Vallance^1*

Division of Gastroenterology, BC's Children's Hospital,¹ Michael Smith Laboratories,² Department of Cellular and Physiological Sciences, Division of Anatomy and Cell Biology, University of British Columbia, Vancouver, British Columbia, Canada³

Received 17 January 2007/ Returned for modification 8 March 2007/ Accepted 27 October 2007

The attaching and effacing (A/E) bacterial pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli and the related mouse pathogen Citrobacter rodentium colonize their hosts' intestines by infecting the apical surfaces of enterocytes, subverting their function, and they ultimately cause diarrhea. Surprisingly, little is known about the interactions of these organisms with goblet cells, which are specialized epithelial cells that secrete the protective molecules Muc2 and trefoil factor 3 (Tff3) into the intestinal lumen. C. rodentium infection leads to dramatic goblet cell depletion within the infected colon, yet it is not clear whether C. rodentium infects goblet cells or if this pathology is pathogen or host mediated. As determined by immunostaining and PCR, both the number of goblet cells and the expression of genes encoding Muc2 and Tff3 were significantly reduced by day 10 postinfection. While electron microscopy and immunostaining revealed that 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 knockout (KO) (T- and B-cell-deficient) mice were infected with C. rodentium. Rag1 KO mice did not exhibit the reduction in the number of goblet cells or in mediator (Muc2 and Tff3) expression observed in infected immunocompetent mice. However, reconstitution of Rag1 KO mice with T and B lymphocytes from C57BL/6 mice restored the goblet cell depletion phenotype during C. rodentium infection. In conclusion, these studies demonstrated 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.

Published ahead of print on 5 November 2007.

Editor: J. F. Urban, Jr.

K.S.B.B. and J.A.G. contributed equally to this work.