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.

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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