Implication of macrophages in blood brain barrier disruption during central nervous system infection

Abstract

Infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces extensive cell infiltration and provides a useful model to study both virus-induced encephalitis and demyelination. Cells recruited into the CNS include components of the innate response, namely neutrophils, NK cells and macrophages, followed by CD4, CD8 T cells and B cells. CD8 T cells are the primary effectors which control virus replication. The exact contribution of macrophages in JHMV pathogenesis remains unclear. Pathogenesis studies in CCR5 deficient mice (a chemokine receptor involved in macrophage and T cell recruitment) suggested a role of macrophages in demyelination. In addition, depletion of both neutrophils and monocytes by the antiGr1 antibody (RB6-8C5) significantly reduced blood brain barrier (BBB) permeability and correlated with an absence of matrix metalloproteinase-9 (MMP9) activity. These data suggested a potential role of neutrophils and macrophages in BBB disruption by MMP9 release.