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PMID:16239543

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Citation

Kielian, T, Haney, A, Mayes, PM, Garg, S and Esen, N (2005) Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess. Infect. Immun. 73:7428-35

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 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.

Links

PubMed PMC1273898 Online version:10.1128/IAI.73.11.7428-7435.2005

Keywords

Animals; Antigens, CD14/biosynthesis; Brain Abscess/complications; Brain Abscess/immunology; Brain Abscess/microbiology; Brain Abscess/pathology; Chemokine CXCL2; Chemokines/biosynthesis; Gene Expression Regulation; Inflammation/complications; Inflammation/pathology; Inflammation Mediators/immunology; Inflammation Mediators/metabolism; Interleukin-17/metabolism; Mice; Mice, Knockout; Signal Transduction; Staphylococcal Infections/complications; Staphylococcal Infections/immunology; Staphylococcal Infections/pathology; Toll-Like Receptor 2/deficiency; Toll-Like Receptor 2/genetics; Toll-Like Receptor 2/immunology; Toll-Like Receptor 2/metabolism; Tumor Necrosis Factor-alpha/biosynthesis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TNFA

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CXCL2

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:IL17

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

  • regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032722: positive regulation of chemokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

  • regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032700: negative regulation of interleukin-17 production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

  • regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0045429: positive regulation of nitric oxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

  • regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TNFA

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CXCL2

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032722: positive regulation of chemokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0032700: negative regulation of interleukin-17 production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0042535: positive regulation of tumor necrosis factor biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0045429: positive regulation of nitric oxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

regulates_o_occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:TLR2

acts_upstream_of_or_within

GO:0052063: induction by symbiont of defense-related host nitric oxide production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2178675

P

has_participant:(EMAPA:16894)

Seeded From UniProt

complete


See also

References

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