Lipopolysaccharide-binding protein increases toll-like receptor 4-dependent activation by nontypeable Haemophilus influenzae.
Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract infections. This study investigated the ability of NTHi to bind lipopolysaccharide-binding protein (LBP) derived from respiratory epithelial cells and the subsequent stimulation of transfected cells expressing membrane-bound CD14 and toll-like receptor 2 (TLR2) or TLR4. In the absence of LBP, NTHi at high concentrations (100 bacteria/epithelial cell) were required to induce signals through TLR2 and TLR4. Flow cytometry showed that NTHi in the stationary phase bound more LBP than did log-phase bacteria. Of interest, as few as 1 LBP-bearing bacterium/cell induced strong signaling through TLR4. In contrast, LBP bound to NTHi did not promote any increased signaling mediated by TLR2, compared with NTHi without LBP. These data suggest that, upon NTHi infection, low numbers of bacteria binding LBP may activate TLR4-bearing cells, such as alveolar macrophages, and consequently induce an inflammatory response.
Lazou Ahrén
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I
Department of Medical Microbiology, Malmö University Hospital, Sweden.
Bjartell
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Egesten
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Riesbeck
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K
D000209:Acute-Phase Proteins / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins; D006193:Haemophilus influenzae / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein; C495342:TLR2 protein, human; C495345:TLR4 protein, human