The protein family TcTASV-C is a novel Trypanosoma cruzi virulence factor secreted in extracellular vesicles by trypomastigotes and highly expressed in bloodstream forms

PLoS Negl Trop Dis. 2018 May 4;12(5):e0006475. doi: 10.1371/journal.pntd.0006475. eCollection 2018 May.

Abstract

TcTASV-C is a protein family of about 15 members that is expressed only in the trypomastigote stage of Trypanosoma cruzi. We have previously shown that TcTASV-C is located at the parasite surface and secreted to the medium. Here we report that the expression of different TcTASV-C genes occurs simultaneously at the trypomastigote stage and while some secreted and parasite-associated products are found in both fractions, others are different. Secreted TcTASV-C are mainly shedded through trypomastigote extracellular vesicles, of which they are an abundant constituent, despite its scarce expression on culture-derived trypomastigotes. In contrast, TcTASV-C is highly expressed in bloodstream trypomastigotes; its upregulation in bloodstream parasites was observed in different T. cruzi strains and was specific for TcTASV-C, suggesting that some host-molecules trigger TcTASV-C expression. TcTASV-C is also strongly secreted by bloodstream parasites. A DNA prime-protein boost immunization scheme with TcTASV-C was only partially effective to control the infection in mice challenged with a highly virulent T. cruzi strain. Vaccination triggered a strong humoral response that delayed the appearance of bloodstream trypomastigotes at the early phase of the infection. Linear epitopes recognized by vaccinated mice were mapped within the TcTASV-C family motif, suggesting that blockade of secreted TcTASV-C impacts on the settlement of infection. Furthermore, although experimental and naturally T. cruzi-infected hosts did not react with antigens from extracellular vesicles, vaccinated and challenged mice recognized not only TcTASV-C but also other vesicle-antigens. We hypothesize that TcTASV-C is involved in the establishment of the initial T. cruzi infection in the mammalian host. Altogether, these results point towards TcTASV-C as a novel secreted virulence factor of T. cruzi trypomastigotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood / parasitology*
  • Chagas Disease / blood
  • Chagas Disease / metabolism
  • Chagas Disease / parasitology*
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / parasitology*
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Multigene Family
  • Protein Transport
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Trypanosoma cruzi / genetics
  • Trypanosoma cruzi / growth & development*
  • Trypanosoma cruzi / metabolism*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Protozoan Proteins
  • Virulence Factors

Grant support

This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica/ Fondo para la Investigación Científica y Tecnológica -ANPCyT/FONCyT- (PICT-2014-1151; http://www.agencia.mincyt.gob.ar/frontend/agencia/post/1833- and PICT-2016-0108, http://www.agencia.mincyt.gob.ar/frontend/agencia/convocatoria/369) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP-2015-186; http://convocatorias.conicet.gov.ar/investigacion-y-desarrollo/) -both from Argentina- to VT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.