title: Role of Toll-like receptor 2 in innate resistance to Group B Streptococcus.
abstract: The Gram-positive bacterium Group B Streptococcus (GBS) is an important cause of serious neonatal and adult infections. Toll-like receptor 2 (TLR2) recognizes components of the cell wall of Gram-positive bacteria and is critical for defense against certain invasive pathogens. In GBS, penicillin-binding protein 1a (PBP1a), encoded by ponA, is required for virulence. PBPs participate in cell wall synthesis and in previous studies; the absence of PBP1a was shown to result in subtle changes in the cell wall ultrastructure. Here, we examine the role of TLR2 in defense against GBS infection and the impact of mutation of ponA on TLR2-mediated host responses. We demonstrate TLR2-recognition of both wild-type (WT) GBS and the ponA mutant in vitro. TLR2(-/-) mice were significantly more susceptible than WT mice to infection with either strain of GBS, indicating a crucial role for TLR2 in defense against GBS. Additionally, the ponA mutant was severely attenuated for virulence in both strains of mice. The mutation in ponA did not affect cytokine expression by WT or TLR2(-/-) mice. These data indicate that TLR2 is required for host defense against GBS and this response is unaffected by the absence of PBP1a and the resultant changes in cell wall ultrastructure.
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, Children's Hospital and Regional Medical Center, University of Washington, Seattle, WA 98105, USA.
authors.forename: Iain R
authors.initials: IR
authors.lastname: Asplin
authors.forename: David J
authors.initials: DJ
authors.lastname: Carl
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Jones
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D009154:Mutation / Q000276:immunology; D013292:Streptococcus agalactiae / Q000235:genetics / Q000472:pathogenicity*; D016019:Survival Analysis; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha