Reduced macrophage infiltration and demyelination in mice lacking the chemokine receptor CCR5 following infection with a neurotropic coronavirus.
Studies were performed to investigate the contributions of the CC chemokine receptor CCR5 in host defense and disease development following intracranial infection with mouse hepatitis virus (MHV). T cell recruitment was impaired in MHV-infected CCR5(-/-) mice at day 7 postinfection (pi), which correlated with increased (P < or = 0.03) titers within the brain. However, by day 12 pi, T cell infiltration into the CNS of infected CCR5(-/-) and CCR5(+/+) mice was similar and both strains exhibited comparable viral titers, indicating that CCR5 expression is not essential for host defense. Following MHV infection of CCR5(+/+) mice, greater than 50% of cells expressing CCR5 antigen were activated macrophage/microglia (determined by F4/80 antigen expression). In addition, infected CCR5(-/-) mice exhibited reduced (P < or = 0.02) macrophage (CD45(high)F4/80(+)) infiltration, which correlated with a significant reduction (P < or = 0.001) in the severity of demyelination compared to CCR5(+/+) mice. These data indicate that CCR5 contributes to MHV-induced demyelination by allowing macrophages to traffic into the CNS.
Glass
W G
WG
Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697-3900, USA.
Liu
M T
MT
Kuziel
W A
WA
Lane
T E
TE
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology*; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology; D018792:Encephalitis, Viral / Q000276:immunology* / Q000473:pathology; D006524:Hepatitis, Viral, Animal / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000302:isolation & purification / Q000502:physiology*; D009186:Myelin Sheath / Q000473:pathology; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014779:Virus Replication
D019713:Receptors, CCR5