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 journalArticle

197 Citations (Scopus)

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

Fingerprint

Astrocytes
Toll-Like Receptors
Interleukin-6
Central Nervous System Viral Diseases
Toll-Like Receptor 1
Ligands
Flagellin
Chemokine CCL5
Peptidoglycan
Chemokine CCL2
Blood-Brain Barrier
Interleukin-1
Chemokines
Innate Immunity
Dendritic Cells
human TLR3 protein
Monocytes
Protein Isoforms
B-Lymphocytes
Central Nervous System

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Preferential expression and function of Toll-like receptor 3 in human astrocytes. / Farina, Cinthia; Krumbholz, Markus; Giese, Thomas; Hartmann, Gunther; Aloisi, Francesca; Meinl, Edgar.

In: Journal of Neuroimmunology, Vol. 159, No. 1-2, 02.2005, p. 12-19.

Research output: Contribution to journalArticle

Farina, Cinthia ; Krumbholz, Markus ; Giese, Thomas ; Hartmann, Gunther ; Aloisi, Francesca ; Meinl, Edgar. / Preferential expression and function of Toll-like receptor 3 in human astrocytes. In: Journal of Neuroimmunology. 2005 ; Vol. 159, No. 1-2. pp. 12-19.
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