Preferential expression and function of Toll-like receptor 3 in human astrocytes

Cinthia Farina, Markus Krumbholz, Thomas Giese, Gunther Hartmann, Francesca Aloisi, Edgar Meinl

Research output: Contribution to journalArticlepeer-review

Abstract

In contrast to other tissues, the central nervous system (CNS) is essentially devoid of MHC expression and shielded from antibodies by the blood-brain barrier. Therefore, a rapid local innate immune response by resident brain cells is required to effectively fight infectious agents. This study analyzed the expression and function of Toll-like receptors (TLRs) in cultured human astrocytes. Quantitative PCR for TLRs 1 to 10 showed a basal expression of TLR3 that could be enhanced by IFN-γ, IL-1β, and IFN-β. The other TLRs were barely detectable and not inducible by the same cytokines. IFN-γ-activated astrocytes responded to TLR3 ligand poly (I:C) engagement with IL-6 production, while ligands of other TLRs, like LPS, lipoteichoic acid, peptidoglycan, flagellin, and CpG, had no effect. Poly (I:C) also triggered astrocyte production of TNF-α and the chemokines CCL2/MCP-1, CCL5/RANTES, CCL20/MIP-3α, and CXCL10/IP-10. The adapter molecules MyD88 (full length and short isoform), TIRAP/Mal, and TICAM-1/TRIF, which are required for TLR signaling, were all expressed by astrocytes. Thus, resting and activated human astrocytes express preferentially TLR3 and, upon TLR3 engagement, produce IL-6 and chemokines active on T cells, B cells, monocytes, and dendritic cells. These data indicate that astrocytes function as sentinels for viral infections in the CNS.

Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalJournal of Neuroimmunology
Volume159
Issue number1-2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Central nervous system
  • Chemokines
  • Glial cells
  • Inflammation
  • Innate immunity

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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