The immunosuppressive effects of a novel recombinant LipQ (Rv2485c) protein of Mycobacterium tuberculosis on human macrophage cell lines

Microb Pathog. 2017 Jun:107:361-367. doi: 10.1016/j.micpath.2017.04.015. Epub 2017 Apr 12.

Abstract

Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro.Our results demonstrate that rLipQ significantly lowers the expression level of pro-inflammatory cytokines (TNF-α& IFN-γ) and augments the level of anti inflammatory cytokines such as IL-4 & IL-10as compared to LPS stimulated macrophages. An up-regulation of anti-inflammatory and down-regulation of pro-inflammatory cytokines levels in rLipQ pretreated macrophages implies immuno-modulatory functions in TB patients. Interestingly, rLipQ also inhibited the expression of iNOS, TLR-2 and transcription factor NF-kB in LPS stimulated macrophages whereas the expression of TLR-4 remains unchanged. The inhibition in the expression of these signaling molecules has been correlated to the inhibition of NO production in macrophages. Taken together, these studies demonstrate that rLipQ is a novel lipase that is highly immunogenic and may play an important role in the virulence and pathogenesis of M. tuberculosis infection, by altering the balance of cytokines, which might help to assess prognosis and contribute to a better understanding against host-pathogen interactions.

Keywords: Cytokines; Lipase; Mycobacterium tuberculosis.

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Down-Regulation
  • Host-Pathogen Interactions
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Lipase / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / microbiology
  • Mycobacterium tuberculosis / metabolism*
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Recombinant Proteins / genetics*
  • Recombinant Proteins / pharmacology*
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4 / metabolism
  • Tuberculosis / microbiology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • Cytokines
  • IL10 protein, human
  • IL4 protein, human
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • NF-kappa B
  • Recombinant Proteins
  • Rv2468c protein, Mycobacterium tuberculosis
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Nitric Oxide
  • Interferon-gamma
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Lipase