Dynamic flux of microvesicles modulate parasite-host cell interaction of Trypanosoma cruzi in eukaryotic cells

Cell Microbiol. 2017 Apr;19(4). doi: 10.1111/cmi.12672. Epub 2016 Nov 11.

Abstract

Extracellular vesicles released from pathogens may alter host cell functions. We previously demonstrated the involvement of host cell-derived microvesicles (MVs) during early interaction between Trypanosoma cruzi metacyclic trypomastigote (META) stage and THP-1 cells. Here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. First, we observed that infective host cell-derived trypomastigote (tissue culture-derived trypomastigote [TCT]), META, and noninfective epimastigote (EPI) stages were able to induce different levels of MV release from THP-1 cells; however, only META and TCT could increase host cell invasion. Fluorescence resonance energy transfer microscopy revealed that THP-1-derived MVs can fuse with parasite-derived MVs. Furthermore, MVs derived from the TCT-THP-1 interaction showed a higher fusogenic capacity than those from META- or EPI-THP-1 interaction. However, a higher presence of proteins from META (25%) than TCT (12%) or EPI (5%) was observed in MVs from parasite-THP-1 interaction, as determined by proteomics. Finally, sera from patients with chronic Chagas disease at the indeterminate or cardiac phase differentially recognized antigens in THP-1-derived MVs resulting only from interaction with infective stages. The understanding of intracellular trafficking and the effect of MVs modulating the immune system may provide important clues about Chagas disease pathophysiology.

Keywords: Chagas disease; Trypanosoma cruzi; extracellular vesicles; innate immunity; microvesicles; parasite-host cell interaction.

MeSH terms

  • Animals
  • Antigens, Protozoan / immunology
  • Cell-Derived Microparticles / metabolism*
  • Cell-Derived Microparticles / parasitology
  • Chagas Disease / immunology
  • Chagas Disease / metabolism
  • Chagas Disease / parasitology*
  • Chlorocebus aethiops
  • Host-Parasite Interactions
  • Humans
  • Membrane Fusion
  • Mice, Inbred BALB C
  • Monocytes / metabolism
  • Monocytes / parasitology*
  • Proteome / metabolism
  • Trypanosoma cruzi / physiology*
  • Vero Cells

Substances

  • Antigens, Protozoan
  • Proteome