Mycobacterial glycolipids di-O-acylated trehalose and tri-O-acylated trehalose downregulate inducible nitric oxide synthase and nitric oxide production in macrophages

BMC Immunol. 2015 Jun 23:16:38. doi: 10.1186/s12865-015-0102-3.

Abstract

Background: Tuberculosis (TB) remains a serious human health problem that affects millions of people in the world. Understanding the biology of Mycobacterium tuberculosis (Mtb) is essential for tackling this devastating disease. Mtb possesses a very complex cell envelope containing a variety of lipid components that participate in the establishment of the infection. We have previously demonstrated that di-O-acylated trehalose (DAT), a non-covalently linked cell wall glycolipid, inhibits the proliferation of T lymphocytes and the production of cytokines.

Results: In this work we show that DAT and the closely related tri-O-acylated trehalose (TAT) inhibits nitric oxide (NO) production and the inducible nitric oxide synthase (iNOS) expression in macrophages (MØ).

Conclusions: These findings show that DAT and TAT are cell-wall located virulence factors that downregulate an important effector of the immune response against mycobacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation / drug effects
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Down-Regulation / drug effects
  • Glycolipids / isolation & purification
  • Glycolipids / pharmacology*
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Mice, Inbred BALB C
  • Mycobacterium / chemistry*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase Type II / metabolism*
  • Trehalose / isolation & purification
  • Trehalose / pharmacology*

Substances

  • Glycolipids
  • Lipopolysaccharides
  • Nitric Oxide
  • Interferon-gamma
  • Trehalose
  • Nitric Oxide Synthase Type II