title: The chemokine CCL5 is essential for leukocyte recruitment in a model of severe Herpes simplex encephalitis.
abstract: The Herpes simplex virus-1 (HSV-1) is responsible for several clinical manifestations in humans, including encephalitis. To induce encephalitis, C57BL/6 mice were inoculated with 10(4) plaque-forming cells of HSV-1 by the intracranial route. Met-RANTES (regulated upon activation, normal T cell expressed and presumably secreted) (10 microg/mouse), a CC chemokine family receptor (CCR)1 and CCR5 antagonist, was given subcutaneously the day before, immediately after, and at days 1, 2, and 3 after infection. Treatment with Met-RANTES had no effect on the viral titers. In contrast, intravital microscopy revealed that treatment with Met-RANTES decreased the number of leukocytes adherent to the pial microvasculature at days 1 and 3 after infection. The levels of the chemokines CCL3, CCL5, CXCL1, and CXCL9 increased after infection and were enhanced further by the treatment with Met-RANTES. Treatment with a polyclonal anti-CCL5 antibody 2 h before the intravital microscopy decreased leukocyte adhesion in the microcirculation of infected mice. In conclusion, CCL5, a chemokine that binds to CCR1 and CCR5, is essential for leukocyte adhesion during HSV-1 encephalitis. However, blocking of CCR1 and CCR5 did not affect HSV-1 replication, suggesting that other immune mechanisms are involved in the process of infection control.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Márcia Carvalho
authors.initials: MC
authors.lastname: Vilela
authors.forename: Daniel Santos
authors.initials: DS
authors.lastname: Mansur
authors.forename: Norinne
authors.initials: N
authors.lastname: Lacerda-Queiroz
authors.forename: David Henrique
authors.initials: DH
authors.lastname: Rodrigues
authors.forename: Graciela Kunrath
authors.initials: GK
authors.lastname: Lima
authors.forename: Rosa Maria Esteves
authors.initials: RM
authors.lastname: Arantes
authors.forename: Erna Geessien
authors.initials: EG
authors.lastname: Kroon
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: da Silva Campos
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018946:Chemokine CCL5 / Q000276:immunology* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004727:Endothelium / Q000187:drug effects / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D008578:Meninges / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D014709:Vero Cells; D019562:Viral Load
chemical_list: D000906:Antibodies; D018946:Chemokine CCL5; C108335:RANTES, Met-