Open AccessCritical Role of Lipopolysaccharide-Binding Protein and CD14 in Immune Responses against Gram-Negative Bacteria
Author(s) -
Didier Le Roy,
Franco Di Padova,
Yoshiyuki Adachi,
M. P. Glauser,
Thierry Calandra,
Didier Heumann
Publication year - 2001
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.167.5.2759
Subject(s) - cd14 , lipopolysaccharide binding protein , lipopolysaccharide , microbiology and biotechnology , virulence , tumor necrosis factor alpha , innate immune system , immune system , klebsiella pneumoniae , sepsis , immunity , bacteria , biology , escherichia coli , immunology , biochemistry , genetics , gene
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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