Traffic of leukocytes in the central nervous system is associated with chemokine up-regulation in a severe model of herpes simplex encephalitis: an intravital microscopy study.
Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The development of experimental models of HSV-1 encephalitis is relevant for the comprehension of the immune mechanisms involved in this infection. C57BL/6 mice were inoculated intracranially with 10(4) PFU of neurotropic HSV-1. All animals developed signs of encephalitis and died until day 6 post-infection (pi). Using intravital microscopy, we demonstrated increased leukocyte rolling and adhesion in the brain microvasculature of infected mice at days 1, 3 and 5 pi. The infection was followed by a significant increase in chemokine levels, including CCL2, CCL3, CCL5, CXCL1 and CXCL9. TNF-alpha also showed a significant increase at day 3 pi. Histological analyses demonstrated diffuse meningoencephalitis characterized mainly by mononuclear cell infiltrates. The present model of HSV-1 encephalitis exhibits high mortality in the very first days of infection. Accordingly, there were increased rolling and adhesion of leukocytes along the brain endothelium wall and a high expression of chemokines in the central nervous system. These results corroborate the role of chemokines in leukocyte recruitment following HSV-1 infection in the central nervous system.
Vilela
Márcia Carvalho
MC
Pós-Graduação em Infectologia e Medicina Tropical, Faculdade de Medicina (FM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Mansur
Daniel Santos
DS
Lacerda-Queiroz
Norinne
N
Rodrigues
David Henrique
DH
Arantes
Rosa Maria Esteves
RM
Kroon
Erna Geessien
EG
Campos
Marco Antônio
MA
Teixeira
Mauro Martins
MM
Teixeira
Antônio Lúcio
AL
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002490:Central Nervous System / Q000473:pathology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000378:metabolism / Q000473:pathology*; D004727:Endothelium / Q000473:pathology; D018259:Herpesvirus 1, Human; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
D018925:Chemokines