Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection

Nat Microbiol. 2016 Oct 17;2:16191. doi: 10.1038/nmicrobiol.2016.191.

Abstract

The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production. Administration of FL-WRS into Salmonella typhimurium-infected mice reduced the levels of bacteria and improved mouse survival, whereas its titration with the specific antibody aggravated the infection. The N-terminal 154-amino-acid eukaryote-specific peptide of WRS was sufficient to recapitulate FL-WRS activity and its interaction mode with TLR4-MD2 is now suggested. Based on these results, secretion of FL-WRS appears to work as a primary defence system against infection, acting before full activation of innate immunity.

MeSH terms

  • Animals
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • Bacterial Load
  • Chemokines / metabolism
  • Humans
  • Immunity, Innate*
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / blood
  • Immunologic Factors / metabolism*
  • Macrophages / immunology
  • Mice
  • Monocytes / immunology
  • Phagocytosis
  • Salmonella Infections, Animal
  • Salmonella typhimurium / isolation & purification
  • Sepsis / immunology
  • Sepsis / pathology
  • Survival Analysis
  • Tryptophan-tRNA Ligase / administration & dosage
  • Tryptophan-tRNA Ligase / blood
  • Tryptophan-tRNA Ligase / metabolism*

Substances

  • Chemokines
  • Immunologic Factors
  • Tryptophan-tRNA Ligase