TY - GEN
T1 - The chemokine CCL5 is essential for leukocyte recruitment in a model of severe Herpes simplex encephalitis
AU - Vilela, Márcia Carvalho
AU - Mansur, Daniel Santos
AU - Lacerda-Queiroz, Norinne
AU - Rodrigues, David Henrique
AU - Lima, Graciela Kunrath
AU - Arantes, Rosa Maria Esteves
AU - Kroon, Erna Geessien
AU - Da Silva Campos, Marco Antônio
AU - Teixeira, Mauro Martins
AU - Teixeira, Antônio Lúcio
PY - 2009/2
Y1 - 2009/2
N2 - 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 μg/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.
AB - 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 μg/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.
KW - CCL5
KW - Encephalitis
KW - Herpes virus
KW - Intravital microscopy
KW - Met-RANTES
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U2 - 10.1111/j.1749-6632.2008.03959.x
DO - 10.1111/j.1749-6632.2008.03959.x
M3 - Conference contribution
C2 - 19236348
AN - SCOPUS:60349100366
SN - 9781573317467
T3 - Annals of the New York Academy of Sciences
SP - 256
EP - 263
BT - Neuroimmunomodulation
PB - Blackwell Publishing Inc.
ER -