| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
¶
*Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212;
Department of Medicine,
Department of Pathology,
Department of Cancer Biology, and
¶Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Th17-driven immune responses contribute to the pathogenesis of many chronic inflammatory diseases. In this study, we investigated the role of IL-17 signaling in chronic gastric inflammation induced by Helicobacter pylori, a Gram-negative bacterium that persistently colonizes the human stomach. Wild-type C57BL/6 mice and mice lacking IL-17RA (IL-17RA–/–) were orogastrically infected with H. pylori. Differences in bacterial colonization density and gastric inflammation were not apparent at 1 mo postinfection, but by 3 mo postinfection, H. pylori colonization density was higher and mononuclear gastric inflammation more severe in infected IL-17RA–/– mice than in infected wild-type mice. A striking feature was a marked increase in gastric B cells, plasma cells, and lymphoid follicles, along with enhanced H. pylori-specific serum Ab responses, in infected IL-17RA–/– mice. Fewer gastric neutrophils and lower levels of neutrophil-recruiting chemokines were detected in infected IL-17RA–/– mice than in infected wild-type mice. Gastric IL-17a and IL-21 transcript levels were significantly higher in infected IL-17RA–/– mice than in infected wild-type mice or uninfected mice, which suggested that a negative feedback loop was impaired in the IL-17RA–/– mice. These results underscore an important role of IL-17RA signaling in regulating B cell recruitment. In contrast to many chronic inflammatory diseases in which IL-17RA signaling promotes an inflammatory response, IL-17RA signaling down-regulates the chronic mononuclear inflammation elicited by H. pylori infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Medical Research Service of the Department of Veterans Affairs and by Grants R01AI39657, R01AI068009, and R0I DK58587 from the National Institutes of Health. The Vanderbilt Medical Center Flow Cytometry Shared Resource is supported by Grant P30 CA68485 from the Vanderbilt Ingram Cancer Center and Grant P30 DK058404 from the Vanderbilt Digestive Disease Research Center. Research Histology Core Services were supported by the Vanderbilt Digestive Disease Research Center.
2 Address correspondence and reprint requests Dr. Holly M. Scott Algood, Division of Infectious Disease, Vanderbilt University School of Medicine, A2200 Medical Center North, Nashville, TN 37232. E-mail address: holly.m.algood{at}vanderbilt.edu
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
