Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria.
LPS-binding protein (LBP) and CD14 potentiate cell activation by LPS, contributing to lethal endotoxemia. We analyzed the contribution of LBP/CD14 in models of bacterial infection. Mice pretreated with mAbs neutralizing CD14 or LBP showed a delay in TNF-alpha production and died of overwhelming infection within 24 h, after a challenge with 250 CFU of virulent Klebsiella pneumoniae. Blockade of TNF-alpha also increased lethality, whereas pretreatment with TNF-alpha protected mice, even in the presence of LBP and CD14 blockade. Anti-LBP or anti-CD14 mAbs did not improve or decrease lethality with a higher inoculum (10(5) K. pneumoniae) and did not affect outcome following injections of low or high inocula of Escherichia coli O111. These results point to the essential role of LBP/CD14 in innate immunity against virulent bacteria.
Le Roy
D
D
Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois-Lausanne, Lausanne, Switzerland.
Di Padova
F
F
Adachi
Y
Y
Glauser
M P
MP
Calandra
T
T
Heumann
D
D
D000209:Acute-Phase Proteins; D000818:Animals; D000911:Antibodies, Monoclonal; D016470:Bacteremia / Q000209:etiology / Q000276:immunology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D019446:Endotoxemia / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology* / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000276:immunology / Q000472:pathogenicity; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000633:toxicity; D008562:Membrane Glycoproteins; D051379:Mice; D009500:Neutralization Tests; D009504:Neutrophils / Q000276:immunology; D018805:Sepsis / Q000209:etiology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014774:Virulence; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein