Resistance of chemokine receptor 6-deficient mice to Yersinia enterocolitica infection: evidence of defective M-cell formation in vivo.
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.
Westphal
Sabine
S
Department of Medicine B, University of Muenster, Albert-Schweitzer Strasse 33, D-48149 Muenster, Germany.
Lügering
Andreas
A
von Wedel
Julia
J
von Eiff
Christof
C
Maaser
Christian
C
Spahn
Thomas
T
Heusipp
Gerhard
G
Schmidt
M Alexander
MA
Herbst
Hermann
H
Williams
Ifor R
IR
Domschke
Wolfram
W
Kucharzik
Torsten
T
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D044082:Citrobacter rodentium; D003092:Colitis / Q000382:microbiology; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000002:abnormalities / Q000166:cytology* / Q000502:physiology*; D054399:Receptors, CCR6 / Q000235:genetics*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D015009:Yersinia Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015008:Yersinia enterocolitica
C498126:CCR6 protein, mouse; D054399:Receptors, CCR6