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, contr ibuting 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 infe ction within 24 h, after a challenge with 250 CFU of virulent Klebsiella pn eumoniae. Blockade of TNF-alpha also increased lethality, whereas pretreatm ent with TNF-alpha protected mice, even in the presence of LBP and CD14 blo ckade. Anti-LBP or anti-CD14 mAbs did not improve or decrease lethality wit h a higher inoculum (10(5) K. pneumoniae) and did not affect outcome follow ing injections of low or high inocula of Escherichia coli O111. These resul ts point to the essential role of LBP/CD14 in innate immunity against virul ent bacteria.