Differential activation of astrocytes by innate and adaptive immune stimuli

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Abstract
The immunologic privilege of the central nervous system (CNS) makes it crucial that CNS resident cells be capable of responding rapidly to infection. Astrocytes have been reported to express Toll‐like receptors (TLRs), hallmark pattern recognition receptors of the innate immune system, and respond to their ligation with cytokine production. Astrocytes have also been reported to respond to cytokines of the adaptive immune system with the induction of antigen presentation functions. Here we have compared the ability of TLR stimuli and the adaptive immune cytokines interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) to induce a variety of immunologic functions of astrocytes. We show that innate signals LPS– and poly I:C lead to stronger upregulation of TLRs and production of the cytokines IL‐6 and TNF‐α as well as innate immune effector molecules IFN‐α4, IFN‐β, and iNOS compared with cytokine‐stimulated astrocytes. Both innate stimulation and adaptive stimulation induce similar expression of the chemokines CCL2, CCL3, and CCL5, as well as similar enhancement of adhesion molecule ICAM‐1 and VCAM‐1 expression by astrocytes. Stimulation with adaptive immune cytokines, however, was unique in its ability to induce upregulation of MHC II and the functional ability of astrocytes to activate CD4+ T cells. These results indicate potentially important and changing roles for astrocytes during the progression of CNS infection.