Induction of a novel mechanism of accelerated bacterial clearance by lipopolysaccharide in CD14-deficient and Toll-like receptor 4-deficient mice

J Immunol. 2001 Jan 15;166(2):1075-8. doi: 10.4049/jimmunol.166.2.1075.

Abstract

Despite the lack of a proinflammatory response to LPS, CD14-deficient mice clear Gram-negative bacteria (Escherichia coli 0111) at least 10 times more efficiently than normal mice. In this study, we show that this is due to an early and intense recruitment of neutrophils following the injection of Gram-negative bacteria or LPS in CD14-deficient mice; in contrast, neutrophil infiltration is delayed by 24 h in normal mice. Similar results of early LPS-induced PMN infiltration and enhanced clearance of E. coli were seen in Toll-like receptor (TLR) 4-deficient mice. Furthermore, the lipid A moiety of LPS induced early neutrophil infiltration not only in CD14-deficient and TLR-4-deficient mice, but also in normal mice. In conclusion, the lipid A component of LPS stimulates a unique and critical pathway of innate immune responses that is independent of CD14 and TLR4 and results in early neutrophil infiltration and enhanced bacterial clearance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Cricetinae
  • Drosophila Proteins*
  • Escherichia coli / immunology
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / microbiology*
  • Escherichia coli Infections / prevention & control
  • Injections, Intraperitoneal
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Lipopolysaccharide Receptors / genetics*
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / administration & dosage*
  • Lipopolysaccharides / chemistry
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration / genetics
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / physiology
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • Adjuvants, Immunologic
  • Drosophila Proteins
  • Lipid A
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Re lipopolysaccharide
  • Receptors, Cell Surface
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • monophosphoryl lipid A