NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans

Eur J Immunol. 2012 Apr;42(4):880-9. doi: 10.1002/eji.201142105.

Abstract

A role for the nucleotide-binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL-1β, IL-6, and TNF-α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF-α and IL-6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria-containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides
  • Autophagy-Related Proteins
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / immunology
  • Cathelicidins / biosynthesis
  • Cathelicidins / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Female
  • GTP-Binding Proteins / biosynthesis
  • GTP-Binding Proteins / immunology
  • Gene Expression Regulation / immunology
  • Humans
  • Immunity, Innate*
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / microbiology
  • Macrophages, Alveolar / ultrastructure
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / ultrastructure
  • Nod2 Signaling Adaptor Protein / biosynthesis
  • Nod2 Signaling Adaptor Protein / immunology*
  • Phagosomes / immunology
  • Phagosomes / metabolism
  • Phagosomes / microbiology
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / metabolism

Substances

  • ATG16L1 protein, human
  • Antimicrobial Cationic Peptides
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Cathelicidins
  • Cytokines
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • CAP18 lipopolysaccharide-binding protein
  • GTP-Binding Proteins
  • IRGM protein, human