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Infection and Immunity, July 2008, p. 3304-3311, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00041-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

CCL28 Is Increased in Human Helicobacter pylori-Induced Gastritis and Mediates Recruitment of Gastric Immunoglobulin A-Secreting Cells

Department of Microbiology and Immunology, Institute of Biomedicine, and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Box 435, 405 30 Göteborg, Sweden,¹ Department of Surgery, Institute of Medicine, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden²

Received 11 January 2008/ Returned for modification 23 February 2008/ Accepted 13 April 2008

Human Helicobacter pylori infection gives rise to an active chronic gastritis and is a major risk factor for the development of duodenal ulcer disease and gastric adenocarcinoma. The infection is accompanied by a large accumulation of immunoglobulin A (IgA)-secreting cells in the gastric mucosa, and following mucosal immunization only H. pylori-infected volunteers mounted a B-cell response in the gastric mucosa. To identify the signals for recruitment of gastric IgA-secreting cells, we investigated the gastric production of CCL28 (mucosa-associated epithelial chemokine) and CCL25 (thymus-expressed chemokine) in H. pylori-infected and uninfected individuals and the potential of gastric B-cell populations to migrate toward these chemokines. Gastric tissue from H. pylori-infected individuals contained significantly more CCL28 protein and mRNA than that from uninfected individuals, while CCL25 levels remained unchanged. Chemokine-induced migration of gastric lamina propria lymphocytes isolated from patients undergoing gastric resection was then assessed using the Transwell system. IgA-secreting cells and IgA⁺ memory B cells from H. pylori-infected tissues migrated toward CCL28 but not CCL25, while the corresponding cells from uninfected patients did not. Furthermore, IgG-secreting cells from H. pylori-infected patients did not migrate to CCL28 but instead to CXCL12 (SDF-1). However, chemokine receptor expression did not correlate to the migratory pattern of the different B-cell populations. These studies are the first to show increased CCL28 production during gastrointestinal infection in humans and provide an explanation for the large influx of IgA-secreting cells to the gastric mucosa in H. pylori-infected individuals.

Published ahead of print on 21 April 2008.

Editor: S. R. Blanke