CCR2 and CCR7 promote inflammatory monocyte recruitment through synergistic roles during encephalitic virus infection, but the monocyte response in the brain is dependent on the infecting virus

Inflammatory monocytes (iMO) migrate from the bone marrow to the brain during viral encephalitis. For many viruses, including Herpes simplex virus type-1 (HSV), iMO recruitment is dependent on the chemokine receptor CCR2. However, La Crosse virus (LACV) induces iMO recruitment independent of CCR2. Comparison of iMOs from HSV and LACV-infected mice showed higher expression of the g protein-coupled receptor CCR7 in LACV-induced iMOs. CCR2/CCR7 double knockout mice (DKO) had reduced iMO recruitment following LACV infection compared to CCR2 or CCR7 single knockout mice indicating that each receptor regulated iMO recruitment through complimentary roles. Thus, CCR7 is a novel, synergistic pathway to CCR2-induced iMO recruitment during virus infection. Interestingly, unlike HSV-recruited iMOs, LACV-recruited iMOs did not influence disease and had higher expression of proinflammatory and proapoptotic transcripts but reduced mitotic, phagocytic and phagolysosomal pathway transcripts. These findings indicate that virus-specific activation of iMOs may affect their survival, maturation and functional capabilities.