title: Toll-like receptor 2-dependent and -independent activation of macrophages by group B streptococci.
abstract: Group B streptococcus (GBS), a capsulated gram-positive bacterium, is a major cause of newborn infections. Although the innate immune receptor Toll-like receptor (TLR) 2 has been shown to primarily recognize gram-positive bacterial products, the production of TNF by macrophages treated with heat-killed GBS (HK-GBS) does not depend on TLR2. In this report, we have characterized HK-GBS-induced activation of macrophages derived from wildtype and TLR2-deficient mice. Microarray analysis demonstrated that HK-GBS activation of macrophages induces both TLR2-independent and -dependent signals. While the expression of a major fraction of genes in macrophages induced by HK-GBS does not depend on TLR2, induction of several important molecules involved in host innate immunity such as IL-6, IL-1beta, and lipocalin 2 is severely impaired in the absence of TLR2 signaling. Furthermore, we show that HK-GBS utilizes centrifugation sensitive components to induce rapid activation of TLR2(-/-) macrophages and that HK-GBS-induced activation of macrophages is not mediated through its genomic DNA. Together, our results demonstrate that HK-GBS induces TLR2-dependent antimicrobial gene activation and provide further understanding of the molecular basis of host innate response to GBS infection.
authors.affiliation: Department of Immunology, Duke University Medical Center, Box 3010, Durham, NC 27710, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Draper
authors.forename: Heather N
authors.initials: HN
authors.lastname: Bethea
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D000818:Animals; D006358:Hot Temperature; D007249:Inflammation / Q000276:immunology*; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013292:Streptococcus agalactiae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: C439524:TNF protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha