Impaired lymphoid chemokine-mediated migration due to a block on the chemokine receptor switch in human cytomegalovirus-infected dendritic cells.
Dendritic cell (DC) migration from the site of infection to the site of T-cell priming is a crucial event in the generation of antiviral T-cell responses. Here we present to our knowledge the first functional evidence that human cytomegalovirus (HCMV) blocks the migration of infected monocyte-derived DCs toward lymphoid chemokines CCL19 and CCL21. DC migration is blocked by viral impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules. The inhibition occurs with immediate-early-early kinetics, and viral interference with NF-kappaB signaling is likely to be at least partially responsible for the lack of CCR7 expression. DCs which migrate from the infected cultures are HCMV antigen negative, and consequently they do not stimulate HCMV-specific CD8(+) T cells, while CD4(+)-T-cell activation is not impaired. Although CD8(+) T cells can also be activated by alternative antigen presentation mechanisms, the spatial segregation of naive T cells and infected DCs seems a potent mechanism of delaying the generation of primary CD8(+)-T-cell responses and aiding early viral spread.
Section of Infection and Immunity. Department of Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
Magdalena
M
Moutaftsi
Paul
P
Brennan
Stephen A
SA
Spector
Zsuzsanna
Z
Tabi
D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D002633:Chemotaxis; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000821:virology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016328:NF-kappa B; D054400:Receptors, CCR7; D019707:Receptors, Chemokine