RGD Reference Report - Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess. - Rat Genome Database

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

Authors: Kielian, T  Haney, A  Mayes, PM  Garg, S  Esen, N 
Citation: Kielian T, etal., Infect Immun. 2005 Nov;73(11):7428-35.
RGD ID: 8552881
Pubmed: PMID:16239543   (View Abstract at PubMed)
PMCID: PMC1273898   (View Article at PubMed Central)
DOI: DOI:10.1128/IAI.73.11.7428-7435.2005   (Journal Full-text)

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 TLR2 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.

Disease Annotations    
Brain Abscess  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Tlr2  (toll-like receptor 2)

Genes (Mus musculus)
Tlr2  (toll-like receptor 2)

Genes (Homo sapiens)
TLR2  (toll like receptor 2)

Additional Information