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Lipids From Trypanosoma cruzi Amastigotes of RA and K98 Strains Generate a Pro-inflammatory Response via TLR2/6

Emanuel Bott1,2, Alan B Carneiro3, Guadalupe Gimenez1,2

  • 1Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Frontiers in Cellular and Infection Microbiology
|June 6, 2018
PubMed

Insights

Lipids from Trypanosoma cruzi amastigotes trigger inflammatory responses via Toll-like receptor 2/6 (TLR2/6) signaling. Pre-treatment of parasite lipids reduced this pro-inflammatory effect, suggesting enzymatic modification alters immune activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Parasitology

Background:

  • Microbial lipids act as ligands for Toll-like receptors (TLRs), modulating innate immunity.
  • Trypanosoma cruzi lipids are implicated in host-pathogen interactions and immune modulation.

Purpose of the Study:

  • To investigate the in vitro effects of Trypanosoma cruzi lipid extracts on inflammatory responses.
  • To determine the involvement of TLRs in mediating the inflammatory effects of T. cruzi lipids.

Main Methods:

  • In vitro analysis of lipid extracts from T. cruzi amastigote strains (RA and K98).
  • Macrophage stimulation assays measuring lipid body formation, COX-2 expression, TNF-α, and nitric oxide release.
  • HEK cell assays assessing NF-κB activation and IL-8 release.
  • Analysis of lipid extracts after incubation with parasite hydrolytic enzymes.
  • Gas chromatography-mass spectrometry for total fatty acid analysis.

Main Results:

  • Total lipid extracts from both T. cruzi strains induced lipid body formation, COX-2, TNF-α, nitric oxide, NF-κB activation, and IL-8 release.
  • These pro-inflammatory effects were mediated through a TLR2/6 dependent pathway.
  • Lipid extracts pre-incubated to allow hydrolytic enzyme action showed significantly reduced pro-inflammatory responses.
  • Reduced activity correlated with changes in lysophospholipids and fatty acid content.

Conclusions:

  • T. cruzi lipids play a significant role in inducing pro-inflammatory responses via the TLR2/6 pathway.
  • Enzymatic modification of T. cruzi lipids can attenuate their immunomodulatory potential.
  • These findings contribute to understanding immune modulation in T. cruzi infections and host survival.
Keywords:
TLR2/6Trypanosoma cruzilipidsphospholipase A1pro-inflammatory

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