TY - JOUR
T1 - Canonical type I IFN signaling in simian immunodeficiency virus-infected macrophages is disrupted by astrocyte-secreted CCL2
AU - Zaritsky, Luna Alammar
AU - Gama, Lucio
AU - Clements, Janice E.
PY - 2012/4/15
Y1 - 2012/4/15
N2 - HIV-associated neurologic disorders are a mounting problem despite the advent of highly active antiretroviral therapy. To address mechanisms of HIV-associated neurologic disorders, we used an SIV pigtailed macaque model to study innate immune responses in brain that suppress viral replication during acute infection. We previously reported that during acute infection in brain, noncanonical type I IFN signaling occurs, where IFN-β mRNA is induced while IFN-α is simultaneously suppressed. Two downstream IFN-stimulated genes, MxA and TRAIL, also show differential expression patterns. In this study, we show that differential signaling is due to interactions between macrophages and astrocytes. Astrocytes produce high levels of CCL2 upon SIV infection, which binds to CCR2 receptors on macrophages, leading to a selective suppression of IFN-α and the IFN-stimulated gene TRAIL while simultaneously inducing IFN-β and MxA. The interactions between chemokine and cytokine pathways are a novel finding that may specifically occur in the CNS.
AB - HIV-associated neurologic disorders are a mounting problem despite the advent of highly active antiretroviral therapy. To address mechanisms of HIV-associated neurologic disorders, we used an SIV pigtailed macaque model to study innate immune responses in brain that suppress viral replication during acute infection. We previously reported that during acute infection in brain, noncanonical type I IFN signaling occurs, where IFN-β mRNA is induced while IFN-α is simultaneously suppressed. Two downstream IFN-stimulated genes, MxA and TRAIL, also show differential expression patterns. In this study, we show that differential signaling is due to interactions between macrophages and astrocytes. Astrocytes produce high levels of CCL2 upon SIV infection, which binds to CCR2 receptors on macrophages, leading to a selective suppression of IFN-α and the IFN-stimulated gene TRAIL while simultaneously inducing IFN-β and MxA. The interactions between chemokine and cytokine pathways are a novel finding that may specifically occur in the CNS.
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U2 - 10.4049/jimmunol.1103024
DO - 10.4049/jimmunol.1103024
M3 - Article
C2 - 22407919
AN - SCOPUS:84860346298
SN - 0022-1767
VL - 188
SP - 3876
EP - 3885
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -