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3100-12-31
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THE CHEMOKINE CCL5 IS ESSENTIAL FOR LEUKOCYTE RECRUITMENT IN A MODEL OF SEVERE HERPES SIMPLEX ENCEPHALITIS
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Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clınica Medica. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clınica Medica.Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clınica Medica.Belo Horizonte, MG, Brazil
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 104 plaque-forming cells of HSV-1 by the intracranial route. Met-RANTES (regulated upon activation, normal T cell expressed and presumably secreted) (10 mu g/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 I 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
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