Henneke, PhilippTakeuchi, OsamuMalley, RichardLien, EgilIngalls, Robin R.Freeman, Mason W.Mayadas, Tanya N.Nizet, VictorAkira, ShizuoKasper, Dennis L.Golenbock, Douglas2022-08-232022-08-232002-09-242009-03-10<p>J Immunol. 2002 Oct 1;169(7):3970-7.</p>0022-1767 (Print)10.4049/jimmunol.169.7.397012244198https://hdl.handle.net/20.500.14038/38243Group B streptococci (GBS) vigorously activate inflammatory responses. We reported previously that a secreted GBS "factor" activates phagocytes via Toll-like receptor (TLR)2 and TLR6, but that GBS cell walls activate cells independently of these receptors. We hypothesized that the phagocytic immune functions in response to GBS, such as inflammation, uptake, and elimination of bacteria, occur through a coordinated engagement of TLRs, along with the coreceptors CD14 and CD11b/CD18. Using various knockout mice we show that GBS-induced activation of p38 and NF-kappaB depends upon the expression of the cytoplasmic TLR adapter protein, myeloid differentiation factor 88 (MyD88), but not TLR2 and/or TLR4. Macrophages with deletions of CD14 and complement receptor 3 had a normal cytokine response to whole bacteria, although the response to GBS factor was abrogated in CD14-null cells. The intracellular formation of bactericidal oxygen species proved to be MyD88 dependent; however, uptake of GBS, a prerequisite for intracellular killing by O(2) radicals, occurred independently of MyD88. While deletion of complement receptor 3 greatly diminished the uptake of opsonized GBS, it did not affect the formation of bactericidal O(2) radicals or inflammatory signaling intermediates. We conclude that the inflammatory, bactericidal, and phagocytic responses to GBS occur via parallel but independent processes.en-USAdaptor Proteins, Signal TransducingAnimalsAntigens, CD11bAntigens, CD14Antigens, CD18Antigens, DifferentiationCHO CellsCells, CulturedCricetinaeDNA-Binding Proteins*Drosophila ProteinsHumansIntracellular FluidMacrophage ActivationMacrophages, PeritonealMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88NF-kappa BPhagocytosisReactive Oxygen SpeciesReceptors, Cell SurfaceReceptors, ImmunologicSignal TransductionStreptococcus agalactiaeStreptococcus pneumoniaeToll-Like Receptor 2Toll-Like Receptor 4Toll-Like Receptor 9Toll-Like ReceptorsTumor Necrosis Factor-alphaLife SciencesMedicine and Health SciencesJournal Articlehttps://escholarship.umassmed.edu/oapubs/1118770096oapubs/1118