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

• Published in: Infection and Immunity Vol. 76; no. 7; pp. 3304 - 3311
• Main Authors: Hansson, Malin, Hermansson, Michael, Svensson, Helena, Elfvin, Anders, Hansson, Lars-Erik, Johnsson, Erik, Sjöling, Åsa, Quiding-Järbrink, Marianne
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.07.2008; American Society for Microbiology (ASM)
• Subjects: adenocarcinoma; Adult; Aged; Aged, 80 and over; B-lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bacteriology; Biological and medical sciences; Cell Movement; chemokines; Chemokines, CC; Chemokines, CC - metabolism; cytology; Female; Fundamental and applied biological sciences. Psychology; gastric mucosa; Gastric Mucosa - cytology; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; gastritis; Gastritis - immunology; Gastritis - microbiology; Gastritis - physiopathology; Helicobacter pylori; Helicobacter pylori - pathogenicity; Host Response and Inflammation; Humans; immunization; immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin A, Secretory - metabolism; immunology; Male; messenger RNA; metabolism; Microbiology; Middle Aged; Miscellaneous; pathogenicity; patients; physiopathology; resection; risk factors; Up-Regulation; volunteers; Human; IgA; Spirillales; Helicobacter pylori; Microbiology; Spirillaceae; Bacteria; Digestive diseases; Immunity; Gastric disease; Gastritis
• ISSN: 0019-9567; 1098-5522; 1098-5522
• DOI: 10.1128/IAI.00041-08

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-1α). 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.