The Pattern Recognition Receptors Nod1 and Nod2 Account for Neutrophil Recruitment to the Lungs of Mice Infected With Legionella Pneumophila

Microbes Infect. 2010 Oct;12(11):819-27. doi: 10.1016/j.micinf.2010.05.006. Epub 2010 Jun 2.

Abstract

The intracellular bacterium Legionella pneumophila induces a severe form of pneumonia called Legionnaires diseases, which is characterized by a strong neutrophil (NE) infiltrate to the lungs of infected individuals. Although the participation of pattern recognition receptors, such as Toll-like receptors, was recently demonstrated, there is no information on the role of nod-like receptors (NLRs) for bacterial recognition in vivo and for NE recruitment to the lungs. Here, we employed a murine model of Legionnaires disease to evaluate host and bacterial factors involved in NE recruitment to the mice lungs. We found that L. pneumophila type four secretion system, known as Dot/Icm, was required for NE recruitment as dot/icm mutants fail to trigger NE recruitment in a process independent of bacterial multiplication. By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice. In addition, Rip2-dependent responses were important for cytokine production and bacterial clearance. Collectively, these studies show that Nod1, Nod2, and Rip2 account for generation of innate immune responses in vivo, which are important for NE recruitment and bacterial clearance in a murine model of Legionnaires diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Legionella pneumophila / immunology*
  • Legionnaires' Disease / immunology*
  • Lung / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • Neutrophil Infiltration*
  • Nod1 Signaling Adaptor Protein / deficiency
  • Nod1 Signaling Adaptor Protein / immunology*
  • Nod2 Signaling Adaptor Protein / deficiency
  • Nod2 Signaling Adaptor Protein / immunology*
  • Receptor-Interacting Protein Serine-Threonine Kinases / deficiency
  • Receptor-Interacting Protein Serine-Threonine Kinases / immunology*
  • Receptors, Pattern Recognition / immunology
  • Virulence Factors / immunology

Substances

  • Cytokines
  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse
  • Receptors, Pattern Recognition
  • Virulence Factors
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk2 protein, mouse