Differential roles of TLR2 and TLR4 in the host response to Gram-negative bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria meningitidis.
The inflammatory response to bacterial infections plays an important role in the detection and elimination of invading micro-organisms. Various components of the bacterial cell wall are capable of activating this pro-inflammatory response. In the case of Gram-negative bacteria, lipopolysaccharide (LPS) is the dominant trigger, although other bacterial factors are also capable of activating this systemic inflammatory response. Recently, Toll-like receptors (TLRs) have been implicated in host responses to bacterial pathogens. Specifically, TLR4 mediates LPS responses while TLR2 plays a broader role in the recognition of a variety of bacteria and bacterial antigens. The experiments in this study were designed to examine the role of Gram-negative cell wall components, other than LPS, and their cellular receptors in the host response to infection using an LPS-deficient mutant of Neisseria meningitidis. Although less potent than the parental strain, we found the LPS-deficient mutant to be a capable inducer of the inflammatory response in a variety of cell types. Moreover, cellular activation by this mutant required expression of CD14 and TLR2.
Ingalls
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Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts 02118, USA. ringalls@bu.edu
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Golenbock
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D000818:Animals; D016466:CHO Cells; D002473:Cell Wall / Q000276:immunology; D006224:Cricetinae; D029721:Drosophila Proteins; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection
D029721:Drosophila Proteins; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors