📄 Lack of CCR2 results in increased mortality and impaired leukocyte activation and trafficking following infection of the central nervous system with a neurotropic coronavirus

In the present study, we evaluated the role of CCR2 in a model of viral-induced neurologic disease. An orchestrated expression of chemokines, including the CCR2 ligands monocyte chemoattractant protein-1/CCL2 and monocyte chemoattractant protein-3/CCL7, occurs within the CNS following infection with mouse hepatitis virus (MHV). Infection of mice lacking CCR2 (CCR2-/-) with MHV resulted in increased mortality and enhanced viral recovery from the brain that correlated with reduced (p ≤ 0.04) T cell and macrophage/microglial (determined by F4/80 Ag expression, p ≤ 0.004) infiltration into the CNS. Moreover, MHV-infected CCR2-/- mice displayed a significant decrease in Th1-associated factors IFN-γ (p ≤ 0.001) and RANTES/CCL5 (p ≤ 0.002) within the CNS as compared with CCR2+/+ mice. Further, peripheral CD4+ and CD8+ T cells from immunized CCR2-/- mice displayed a marked reduction in IFN-γ production in response to viral Ag and did not migrate into the CNS of MHV-infected recombination-activating gene (RAG)1-/- mice following adoptive transfer. In addition, macrophage/microglial infiltration into the CNS of RAG1-/- mice receiving CCR2-/- splenocytes was reduced (p ≤ 0.05), which correlated with a reduction in the severity of demyelination (p ≤ 0.001) as compared with RAG1-/- mice receiving splenocytes from CCR2+/+ mice. Collectively, these results indicate an important role for CCR2 in host defense and disease by regulating leukocyte activation and trafficking.

keywords 🔗 present study (186) 🔗 hepatitis virus (437) 🔗 mouse hepatitis (371) 🔗 important role (140) 🔗 adoptive transfer (14) 🔗 results indicate (178)

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