Dendritic cells express CCR7 and migrate in response to CCL19 (MIP-3beta) after exposure to Helicobacter pylori.
Helicobacter pylori infection induces chronic inflammation in the gastric mucosa with a marked increase in the number of lymphoid follicles consisting of infiltrating B and T cells, neutrophils, dendritic cells (DC) and macrophages. It has been suggested that an accumulation of mature DC in the tissue, resulting from a failure of DC to migrate to lymph nodes, may contribute to this chronic inflammation. Migration of DC to lymph nodes is regulated by chemokine receptor CCR7, expressed on mature DC, and the CCR7 ligands CCL19 and CCL21. In this study we analysed the maturation, in vitro migration and cytokine production of human DC after stimulation with live H. pylori. For comparison, DC responses to non-pathogenic Escherichia coli bacteria were also evaluated. Stimulation with H. pylori induced maturation of DC, i.e. up-regulation of the chemokine receptors CCR7 and CXCR4 and the maturation markers HLA-DR, CD80 and CD86. The H. pylori-stimulated DC also induced CD4(+) T-cell proliferation. DC stimulated with H. pylori secreted significantly more interleukin (IL)-12 compared to DC stimulated with E. coli, while E. coli-stimulated DC secreted more IL-10. Despite low surface expression of CCR7 protein following stimulation with H. pylori compared to E. coli, the DC migrated equally well towards CCL19 after stimulation with both bacteria. Thus, we could not detect any failure in the migration of H. pylori stimulated DC in vitro that may contribute to chronic gastritis in vivo, and our results suggest that H. pylori induces maturation and migration of DC to lymph nodes where they promote T cell responses.
Hansson
Malin
M
Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Box 435, 405 30 Göteborg, Sweden.
Lundgren
Anna
A
Elgbratt
Kristina
K
Quiding-Järbrink
Marianne
M
Svennerholm
Ann-Mari
AM
Johansson
Eva-Liz
EL
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D037521:Virulence Factors