Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis

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Ato, M; Stager, S; Engwerda, CR; Kaye, PM; (2002) Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis. Nature immunology, 3 (12). pp. 1185-91. ISSN 1529-2908

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Abstract

Interaction between dendritic cells (DCs) and T cells is essential for the generation of cell-mediated immunity. Here we show that DCs from mice with chronic Leishmania donovani infection fail to migrate from the marginal zone to the periarteriolar region of the spleen. Stromal cells were fewer, which was associated with loss of CCL21 and CCL19 expression. The residual stromal cells and endothelium produced sufficient CCL21 to direct the migration of DCs transferred from naive mice. However, DCs from infected mice had impaired migration both in naive recipients and in vitro, in response to CCL21 and CCL19. Defective localization was attributable to tumor necrosis factor-alpha-dependent, interleukin 10-mediated inhibition of CCR7 expression. Effective immunotherapy was achieved with CCR7-expressing DCs, without the need to identify protective Leishmania antigens. Thus defective DC migration plays a major role in the pathogenesis of this disease and the immunosuppression is mediated, at least in part, through the spatial segregation of DCs and T cells.

Item Type:	Article
Keywords:	Animal, Cell Communication/immunology, Cell Movement/immunology, Chemokines, CC/immunology/metabolism, Dendritic Cells/immunology/pathology, Immunity, Natural/genetics, Immunosuppression, Leishmania donovani, Leishmaniasis, Visceral/etiology/immunology, Ligands, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptors, Chemokine/biosynthesis/genetics/*immunology, Stromal Cells/immunology/pathology, Support, Non-U.S. Gov't, T-Lymphocytes/immunology, Animal, Cell Communication, immunology, Cell Movement, immunology, Chemokines, CC, immunology, metabolism, Dendritic Cells, immunology, pathology, Immunity, Natural, genetics, Immunosuppression, Leishmania donovani, Leishmaniasis, Visceral, etiology, immunology, Ligands, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptors, Chemokine, biosynthesis, genetics, immunology, Stromal Cells, immunology, pathology, Support, Non-U.S. Gov't, T-Lymphocytes, immunology
Faculty and Department:	Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID:	12436111
Web of Science ID:	179467800017
URI:	http://researchonline.lshtm.ac.uk/id/eprint/16447

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