Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria |
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Authors: | Le Roy D Di Padova F Adachi Y Glauser M P Calandra T Heumann D |
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Affiliation: | Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois-Lausanne, Lausanne, Switzerland. |
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Abstract: | 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. |
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