TY - JOUR
T1 - Cytomegalovirus induces cytokine and chemokine production differentially in microglia and astrocytes
T2 - Antiviral implications
AU - Cheeran, Maxim C
AU - Hu, Shuxian
AU - Yager, S. L.
AU - Gekker, G.
AU - Peterson, P. K.
AU - Lokensgard, James R
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Glial cells function as sensors for infection within the brain and produce cytokines to limit viral replication and spread. We examined both cytokine (TNF-α, IL-1β, and IL-6) and chemokine (MCP-1, MIP-lα, RANTES, and IL-8) production by primary human glial cells in response to cytomegalovirus (CMV). Although CMV-infected astrocytes did not produce antiviral cytokines, they generated significant quantities of the chemokines MCP-1 and IL-8 in response to viral infection. On the other hand, supernatants from CMV-stimulated purified microglial cell cultures showed a marked increase in the production of TNF-α and IL-6, as well as chemokines. Supernatants from CMV-infected astrocyte cultures induced the migration of microglia towards chemotactic signals generated from infected astrocytes. Antibodies to MCP-1, but not to MIP-1α, RANTES, or IL-8, inhibited this migratory activity. These findings suggest that infected astrocytes may use MCP-1 to recruit 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 role in defense of the brain against CMV. The host defense function of microglial cells may be directed in part by chemokines, such as MCP-1, produced by infected astrocytes.
AB - Glial cells function as sensors for infection within the brain and produce cytokines to limit viral replication and spread. We examined both cytokine (TNF-α, IL-1β, and IL-6) and chemokine (MCP-1, MIP-lα, RANTES, and IL-8) production by primary human glial cells in response to cytomegalovirus (CMV). Although CMV-infected astrocytes did not produce antiviral cytokines, they generated significant quantities of the chemokines MCP-1 and IL-8 in response to viral infection. On the other hand, supernatants from CMV-stimulated purified microglial cell cultures showed a marked increase in the production of TNF-α and IL-6, as well as chemokines. Supernatants from CMV-infected astrocyte cultures induced the migration of microglia towards chemotactic signals generated from infected astrocytes. Antibodies to MCP-1, but not to MIP-1α, RANTES, or IL-8, inhibited this migratory activity. These findings suggest that infected astrocytes may use MCP-1 to recruit 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 role in defense of the brain against CMV. The host defense function of microglial cells may be directed in part by chemokines, such as MCP-1, produced by infected astrocytes.
KW - Chemokines
KW - Cytokines
KW - Cytomegalovirus
KW - Glia
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U2 - 10.1080/13550280152058799
DO - 10.1080/13550280152058799
M3 - Article
C2 - 11517386
AN - SCOPUS:0034927655
VL - 7
SP - 135
EP - 147
JO - Journal of NeuroVirology
JF - Journal of NeuroVirology
SN - 1355-0284
IS - 2
ER -