title: Role of chemokines in the enhancement of BBB permeability and inflammatory infiltration after rabies virus infection.
abstract: Induction of innate immunity, particularly through the induction of interferon and chemokines, by rabies virus (RABV) infection has been reported to be inversely correlated with pathogenicity. To further investigate the association between the expression of chemokines and RABV infection, laboratory-attenuated RABV (B2C) and wild-type (wt) RABV (DRV) were administered to Balb/c mice intramuscularly. Chemokine expression, inflammatory cell infiltration, and blood-brain barrier (BBB) permeability were evaluated at various time points after infection. At day 3 post-infection (p.i.) there was very little inflammation in the central nervous system (CNS) and BBB permeability did not change in mice infected with either virus when compared with mock-infected mice. At 6 day p.i., infection with B2C induced the expression of inflammatory chemokines and infiltration of inflammatory cells into the CNS, while these changes were minimal in DRV-infected mice. Furthermore, infection with B2C significantly enhanced BBB permeability comparing to infection with DRV. Among the upregulated chemokines, the expression of IP-10 was best correlated with infiltration of inflammatory cells into the CNS and enhancement of BBB permeability. These data indicate that laboratory-attenuated RABV induces expression of chemokines and infiltration of inflammatory cells into the CNS. Upregulation of chemokines by B2C may have triggered the change in BBB permeability, which helps infiltration of inflammatory cells into the CNS, and thus attenuation of RABV.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kuang
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Lackay
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology*; D018925:Chemokines / Q000276:immunology*; D005260:Female; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010539:Permeability / Q000187:drug effects*; D011818:Rabies / Q000276:immunology* / Q000473:pathology*; D011820:Rabies virus / Q000276:immunology*
chemical_list: D018925:Chemokines