Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess

Tammy Kielian, Anessa Haney, Patrick M. Mayes, Sarita Garg, Nilufer Esen

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Toll-like receptor 2 (TLR2) is a pattern recognition receptor (PRR) that plays an important role in innate immune recognition of conserved structural motifs on a wide array of pathogens, including Staphylococcus aureus. To ascertain the functional significance of TLR2 in the context of central nervous system (CNS) parenchymal infection, we evaluated the pathogenesis of S. aureus-induced experimental brain abscess in TLR2 knockout (KO) and wild-type (WT) mice. The expression of several proinflammatory mediators, including inducible nitric oxide synthase, tumor necrosis factor alpha, and macrophage inflammatory protein-2, was significantly attenuated in brain abscesses of TLR2 KO mice compared to WT mice during the acute phase of infection. Conversely, interleukin-17 (IL-17), a cytokine produced by activated and memory T cells, was significantly elevated in lesions of TLR2 KO mice, suggesting an association between innate and adaptive immunity in brain abscess. Despite these differences, brain abscess severity in TLR2 KO and WT animals was similar, with comparable mortality rates, bacterial titers, and blood-brain barrier permeability, implying a role for alternative PRRs. Expression of the phagocytic PRRs macrophage scavenger receptor type AI/AII and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was increased in brain abscesses of both TLK2 KO and WT mice compared to uninfected animals. However, LOX-1 induction in brain abscesses of TLR2 KO mice was significantly attenuated compared to WT animals, revealing that the TLR2-dependent signal(s) influence LOX-1 expression. Collectively, these findings reveal the complex nature of gram-positive bacterial recognition in the CNS which occurs, in part, through engagement of TLR2 and highlight the importance of receptor redundancy for S. aureus detection in the CNS.

Original languageEnglish (US)
Pages (from-to)7428-7435
Number of pages8
JournalInfection and immunity
Volume73
Issue number11
DOIs
StatePublished - Nov 1 2005

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Toll-Like Receptor 2
Brain Abscess
Staphylococcus aureus
Knockout Mice
Wild Animals
Class E Scavenger Receptors
Central Nervous System
Chemokine CXCL2
Pattern Recognition Receptors
Scavenger Receptors
Central Nervous System Infections
Interleukin-17
Adaptive Immunity
Nitric Oxide Synthase Type II
Blood-Brain Barrier
Innate Immunity
Permeability
Tumor Necrosis Factor-alpha
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess. / Kielian, Tammy; Haney, Anessa; Mayes, Patrick M.; Garg, Sarita; Esen, Nilufer.

In: Infection and immunity, Vol. 73, No. 11, 01.11.2005, p. 7428-7435.

Research output: Contribution to journalArticle

Kielian, Tammy ; Haney, Anessa ; Mayes, Patrick M. ; Garg, Sarita ; Esen, Nilufer. / Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess. In: Infection and immunity. 2005 ; Vol. 73, No. 11. pp. 7428-7435.
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