Differential roles of CD14 and toll-like receptors 4 and 2 in murine Acinetobacter pneumonia

Am J Respir Crit Care Med. 2006 Jan 1;173(1):122-9. doi: 10.1164/rccm.200505-730OC. Epub 2005 Oct 6.


Rationale: Acinetobacter baumannii is an opportunistic bacterial pathogen that is increasingly associated with gram-negative nosocomial pneumonia, but the molecular mechanisms that play a role in innate defenses during A. baumannii infection have not been elucidated.

Objective: To gain first insight into the role of CD14 and Toll-like receptors 4 and 2 in host response to A. baumannii pneumonia.

Methods: Respective gene-deficient mice were intranasally infected with A. baumannii, and bacterial outgrowth, lung inflammation, and pulmonary cytokine/chemokine responses were determined. To study the importance of LPS in the inflammatory response, mice were also challenged with A. baumannii LPS.

Measurements and main results: Bacterial counts were increased in CD14 and Toll-like receptor 4 gene-deficient mice, and only these animals developed bacteremia. The pulmonary cytokine/chemokine response was impaired in Toll-like receptor 4 knockout mice and the onset of lung inflammation was delayed. In contrast, Toll-like receptor 2-deficient animals displayed an earlier cell influx into lungs combined with increased macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 concentrations, which was associated with accelerated elimination of bacteria from the pulmonary compartment. Neither CD14 nor Toll-like receptor 4 gene-deficient mice responded to intranasal administration of LPS, whereas Toll-like receptor 2 knockout mice were indistinguishable from wild-type animals.

Conclusions: Our results suggest that CD14 and Toll-like receptor 4 play a key role in innate sensing of A. baumannii via the LPS moiety, resulting in effective elimination of the bacteria from the lung, whereas Toll-like receptor 2 signaling seems to counteract the robustness of innate responses during acute A. baumannii pneumonia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / immunology*
  • Acinetobacter baumannii*
  • Animals
  • Disease Models, Animal
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology*
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Knockout
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / pathology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*


  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4