Cytomegalovirus induces cytokine and chemokine production differentially in microglia and astrocytes: Antiviral implications

Glial cells function as sensors for infection within the brain and produce cytokines to limit viral replication and spread. We examined both cytokine (TNF-alpha, IL-1 beta, and IL-6) and chemokine (MCP-1, MIP-1 alpha, RANTES, and IL-8) production by primary human glial cells in response to cytomegal ovirus (CMV). Although CMV-infected astrocytes did not produce antiviral cy tokines, they generated significant quantities of the chemokines MCP-1 and IL-8 in response to viral infection. On the other hand, supernatants from C MV-stimulated purified microglial cell cultures showed a marked increase in the production of TNF-alpha and IL-6, as well as chemokines. Supernatants from CMV-infected astrocyte cultures induced the migration of microglia tow ards chemotactic signals generated fi om infected astrocytes. Antibodies to MCP-I, but not to MIP-1 alpha, RANTES, or IL-8, inhibited this migratory a ctivity. These findings suggest that infected astrocytes may use MCP-1 to r ecruit antiviral cytokine-producing microglial cells to foci of infection, To test this hypothesis, cocultures of astrocytes and microglial cells were infected with CMV. Viral gene expression in these cocultures was 60% lower than in CMV infected purified astrocyte cultures lacking microglia. These results support the hypothesis that microglia play an important antiviral r ole in defense of the brain against CMV. The host defense function of micro glial cells may be directed in part by chemokines, such as MCP-1, produced by infected astrocytes.