Role of Peyer's patches in the induction of Helicobacter pylori -induced gastritis

doi:10.1073/pnas.0609014104

Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis

Departments of *Microbiology and Immunology and
^§Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan;
Divisions of ^‡Bacterial Infection and
^¶Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; and
^†Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan

Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved April 12, 2007 (received for review October 12, 2006)

Abstract

Helicobacter pylori is a Gram-negative spiral bacterium that causes gastritis and peptic ulcer and has been implicated in the pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Although Th1 immunity is involved in gastritis and the accumulation of H. pylori-specific CD4⁺ T cells in the H. pylori-infected gastric mucosa in human patients, how T cells are primed with H. pylori antigens is unknown because no apparent lymphoid tissues are present in the stomach. We demonstrate here that Peyer's patches (PPs) in the small intestine play critical roles in H. pylori-induced gastritis; no gastritis is induced in H. pylori-infected mice lacking PPs. We also observed that the coccoid form of H. pylori is phagocytosed by dendritic cells in PPs. We propose that H. pylori converts to the coccoid form in the anaerobic small intestine and stimulates the host immune system through PPs.

Footnotes

^‖To whom correspondence should be addressed. E-mail: koyasu{at}sc.itc.keio.ac.jp
Author contributions: S.N., H.K., C.S., and S.K. designed research; S.N., H.M., T.Y., Y.B., K.M., T.N., and T.S. performed research; and S.N., C.S., and S.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0609014104/DC1.
Abbreviations:

DKO,

double knockout;

LP,

lamina propria;

gLP,

gastric LP;

gEC,

gastric epithelial cell;

DC,

dendritic cell;

PPs,

Peyer's patches;

OVA,

ovalbumin;

NK,

natural killer;

APC,

antigen-presenting cell;

β-Rag DKO,

IL-2 receptor β chain (IL-2Rβ)−/−Rag2−/− DKO;

γc-Rag DKO,

cytokine receptor common γ chain (γc)−/−Rag2−/− DKO;

GALT,

gut-associated lymphoid tissue;

ILF,

isolated lymphoid follicle;

BMDC,

bone marrow-derived cell;

SED,

subepithelial dome;

mLN,

mesenteric lymph node.