Blocking CC chemokine receptor (CCR) 1 and CCR5 during herpes simplex virus type 2 infection in vivo impairs host defence and perturbs the cytokine response.
Elimination of viral infections is dependent on rapid recruitment of leucocytes to infected areas. Chemokines constitute a class of cytokines that regulate migration of leucocytes to sites of infection. In this work, the expression and function of CC chemokine receptor (CCR)1 and CCR5 and their ligands during a generalized herpes simplex virus type 2 (HSV-2) infection in mice were studied. Many CCR1 and CCR5 ligands were expressed in infected organs after intraperitoneal infection. In particular, CC chemokine expression in the liver preceded the expression of CCR1 and CCR5, suggesting recruitment of cells bearing these receptors, which correlated with a decrease in viral titres. Administration of Met-RANTES, a CCR1 and CCR5 antagonist, led to impaired antiviral response with significantly higher viral titre in the liver on days 1 and 6 after infection. This observation was accompanied by a decreased and shortened recruitment of natural killer cells to the peritoneum of infected mice treated with the antagonist. Despite this reduced recruitment of antiviral leucocytes in mice receiving Met-RANTES, peritoneal cells from these mice produced markedly enhanced levels of pro-inflammatory cytokines. Altogether, the results suggest that CCR1 and/or CCR5 are important for both viral clearance and eventual control of the immune response.
Sørensen
L N
LN
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
Paludan
S R
SR
D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000276:immunology; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000276:immunology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology
C515300:CCR1 protein, human; D065100:CCR5 Receptor Antagonists; C515301:Ccr1 protein, mouse; D018946:Chemokine CCL5; D016207:Cytokines; C108335:RANTES, Met-; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D009569:Nitric Oxide; D012313:RNA