Published online before print February 7, 2008

This Article Full Text (Rapid PDF) All Versions of this Article: ajpath.2008.070393v1 172/3/671    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Westphal, S. Articles by Kucharzik, T. PubMed PubMed Citation Articles by Westphal, S. Articles by Kucharzik, T.

Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.070393

Accepted for publication November 26, 2007.

Article

Resistance of Chemokine Receptor 6-Deficient Mice to Yersinia Enterocolitica Infection. Evidence of Defective M-Cell Formation in Vivo

Sabine Westphal^*, Andreas Lügering^*, Julia von Wedel^*, Christof von Eiff, Christian Maaser^*, Thomas Spahn^*, Gerhard Heusipp, M. Alexander Schmidt, Hermann Herbst, Ifor R. Williams^¶, Wolfram Domschke^*, and Torsten Kucharzik^*@

From the Department of Medicine B,* and the Institutes of Medical Microbiology and Infectiology, University of Muenster, Muenster, Germany; the Institute of Pathology, Klinikum Neukoelln, Berlin, Germany; and the Department of Pathology and Laboratory Medicine,^¶ Emory University School of Medicine, Atlanta, Georgia

^@ To whom correspondence should be addressed. E-mail: torsten.kucharzik{at}ukmuenster.de.

	Abstract

M cells, specialized cells within Peyer's patches (PPs), are reduced in number in chemokine receptor 6 (CCR6)-deficient mice. The pathogenic microorganism Yersinia enterocolitica exploits M cells for the purpose of mucosal tissue invasion exclusively through PPs. The aim of this study was to evaluate the course of yersiniosis in CCR6-deficient mice and to investigate whether these mice might be used as an in vivo model to determine M-cell function. After oral challenge with Y. enterocolitica, control mice suffered from lethal septic infection whereas CCR6-deficient mice showed very limited symptoms of infection. Immunohistochemical analysis demonstrated PP invasion by Y. enterocolitica in control mice whereas no bacteria could be found in CCR6-deficient mice. In addition, a significant induction of proinflammatory cytokines could be found in control mice whereas proinflammatory cytokine levels in CCR6-deficient mice remained unchanged. In contrast, intraperitoneal infection resulted in severe systemic yersiniosis in both mouse groups. Abrogated oral Y. enterocolitica infection in CCR6-deficient mice demonstrates the importance of CCR6 expression in the physiological and pathological immune responses generated within PPs by influencing M-cell differentiation, underscoring the important role of M cells in the process of microbial uptake. CCR6-deficient mice may therefore represent a suitable model for the study of M-cell function in vivo.