The chemokine CCL5 is essential for leukocyte recruitment in a model of severe Herpes simplex encephalitis.
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.
Vilela
Márcia Carvalho
MC
Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Mansur
Daniel Santos
DS
Lacerda-Queiroz
Norinne
N
Rodrigues
David Henrique
DH
Lima
Graciela Kunrath
GK
Arantes
Rosa Maria Esteves
RM
Kroon
Erna Geessien
EG
da Silva Campos
Marco Antônio
MA
Teixeira
Mauro Martins
MM
Teixeira
Antônio Lúcio
AL
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
D000906:Antibodies; D018946:Chemokine CCL5; C108335:RANTES, Met-