Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5.

Abstract

Dendritic cells (DC) play a key role in the host immune response to infections. Human cytomegalovirus (HCMV) infection can inhibit the maturation of DC and impair their ability to stimulate T cell proliferation and cytotoxicity. In this study, we assessed the effects of HCMV infection on the migratory behavior of human DC. The HCMV strain TB40/E inhibited the migration of immature monocyte-derived DC in response to inflammatory chemokines by 95% 1 day after infection. This inhibition was mediated by early viral replicative events, which significantly reduced the cell-surface expression of CC chemokine receptor 1 (CCR1) and CCR5 by receptor internalization. HCMV infection also induced secretion of the inflammatory chemokines CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1alpha (MIP-1alpha), CCL4/MIP-1beta, and CCL5/regulated on activation, normal T expressed and secreted (RANTES). Neutralizing antibodies for these chemokines reduced the effects of HCMV on chemokine receptor expression and on DC migration by approximately 60%. Interestingly, the surface expression of the lymphoid chemokine receptor CCR7 was not up-regulated after HCMV infection on immature DC, and immature-infected DC did not migrate in response to CCL19/MIP-3beta. These findings suggest that blocking the migratory ability of DC may be a potent mechanism used by HCMV to paralyze the early immune response of the host.

• Authors: Stefania Varani, Giada Frascaroli, Mohammed Homman-Loudiyi, Sari Feld, Maria Paola Landini, Cecilia Söderberg-Nauclér
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 77 Issue 2 Pg. 219-28 (Feb 2005) ISSN: 0741-5400 [Print] United States
• PMID: 15522919 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCR1 protein, human
• Receptors, CCR1
• Receptors, CCR5
• Receptors, Chemokine

Topics

• Cell Movement (immunology)
• Cells, Cultured
• Cytomegalovirus (genetics, immunology)
• Cytomegalovirus Infections (immunology, pathology)
• Dendritic Cells (immunology, physiology, virology)
• Down-Regulation
• Humans
• Receptors, CCR1
• Receptors, CCR5 (biosynthesis, immunology)
• Receptors, Chemokine (biosynthesis, immunology)
• Virus Replication