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Updated: Jul 7, 2026

Purification and Visualization of Lipopolysaccharide from Gram-negative Bacteria by Hot Aqueous-phenol Extraction
Published on: May 28, 2012
Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria
D Le Roy1, F Di Padova, Y Adachi
1Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois-Lausanne, Lausanne, Switzerland.
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.
Insights
LPS-binding protein (LBP) and CD14 are crucial for innate immunity against virulent bacteria like Klebsiella pneumoniae. Blocking these proteins delayed TNF-alpha production, increasing mortality in mice.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- LPS-binding protein (LBP) and CD14 enhance lipopolysaccharide (LPS)-induced cell activation, contributing to endotoxemia.
- Understanding the role of LBP/CD14 in bacterial infections is critical for developing therapeutic strategies.
Purpose of the Study:
- To investigate the contribution of LBP and CD14 in innate immune responses during bacterial infections.
- To evaluate the impact of neutralizing LBP/CD14 antibodies on survival and cytokine production in mouse models.
Main Methods:
- Mice were pretreated with monoclonal antibodies (mAbs) neutralizing CD14 or LBP.
- Mice were challenged with virulent Klebsiella pneumoniae or Escherichia coli.
- Tumor necrosis factor-alpha (TNF-alpha) production and survival rates were monitored.
Main Results:
- Neutralization of CD14 or LBP delayed TNF-alpha production and increased mortality in mice infected with a low dose of K. pneumoniae.
- Blockade of TNF-alpha exacerbated lethality, while TNF-alpha pretreatment conferred protection.
- LBP/CD14 blockade did not significantly alter outcomes with higher K. pneumoniae inocula or with E. coli infections.
Conclusions:
- LBP and CD14 play an essential role in innate immunity against virulent bacterial infections, particularly with low bacterial loads.
- Targeting LBP/CD14 may be a viable strategy for modulating immune responses in specific bacterial infections.
- The role of LBP/CD14 appears context-dependent, varying with bacterial species and inoculum size.
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