Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus

Nilufer Esen, Flobert Y. Tanga, Joyce A. DeLeo, Tammy Kielian

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Astrocytes play an important role in initiating and regulating CNS immune responses through the release of proinflammatory cytokines and chemokines. Here we demonstrate that primary astrocytes are capable of recognizing the Gram-positive bacterium Staphylococcus aureus and its cell wall product peptidoglycan (PGN) and respond by producing numerous proinflammatory mediators including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β), MIP-2, and monocyte chemoattractant protein (MCP-1). Astrocytes have recently been shown to express Toll-like receptor 2 (TLR2), a pattern recognition receptor important for recognizing structural components of various Gram-positive bacteria, fungi, and protozoa. However, the functional significance of TLR2 in mediating astrocyte activation remains unknown. Primary astrocytes from TLR2 knockout mice were used to evaluate the role of TLR2 in astrocyte responses to S. aureus and PGN. The results demonstrate that TLR2 is essential for maximal proinflammatory cytokine and chemokine production, but not phagocytosis, in primary astrocytes following S. aureus and PGN exposure. In addition, both stimuli led to a significant increase in TLR2 mRNA expression in wild-type astrocytes as assessed by real-time quantitative RT-PCR. These findings suggest that astrocytes may play a key role in the initial antibacterial immune response in the CNS through engagement of TLR2.

Original languageEnglish (US)
Pages (from-to)746-758
Number of pages13
JournalJournal of Neurochemistry
Volume88
Issue number3
DOIs
StatePublished - Feb 1 2004

Fingerprint

Toll-Like Receptor 2
Gram-Positive Bacteria
Astrocytes
Staphylococcus aureus
Bacteria
Chemical activation
Peptidoglycan
Chemokines
Chemokine CCL8
Protozoa
Cytokines
Macrophage Inflammatory Proteins
Pattern Recognition Receptors
Chemokine CCL2
Fungi
Interleukin-1
Phagocytosis
Knockout Mice
Cell Wall
Real-Time Polymerase Chain Reaction

Keywords

  • Astrocytes
  • Chemokines
  • Peptidoglycan
  • Proinflammatory cytokines
  • Staphylococcus aureus
  • Toll-like receptor 2

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus. / Esen, Nilufer; Tanga, Flobert Y.; DeLeo, Joyce A.; Kielian, Tammy.

In: Journal of Neurochemistry, Vol. 88, No. 3, 01.02.2004, p. 746-758.

Research output: Contribution to journalArticle

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