Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions

PLoS Negl Trop Dis. 2016 Oct 13;10(10):e0005061. doi: 10.1371/journal.pntd.0005061. eCollection 2016 Oct.

Abstract

Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M. vogae). We demonstrate that ES products but not larval homogenates inhibit the stimuli-driven release of the pro-inflammatory, Th1-inducing cytokine IL-12p70 by murine bone marrow-derived dendritic cells (BMDCs). Within the ES fraction, we biochemically narrowed down the immunosuppressive activity to glycoproteins since active components were lipid-free, but sensitive to heat- and carbohydrate-treatment. Finally, using bioassay-guided chromatographic analyses assisted by comparative proteomics of active and inactive fractions of the ES products, we defined a comprehensive list of candidate proteins released by M. corti tetrathyridia as potential suppressors of DC functions. Our study provides a comprehensive library of somatic and ES products and highlight some candidate parasite factors that might drive the subversion of DC functions to facilitate the persistence of M. corti tetrathyridia in their hosts.

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / parasitology
  • Cestode Infections / immunology*
  • Cestode Infections / parasitology
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics
  • Helminth Proteins / immunology*
  • Humans
  • Larva / chemistry
  • Larva / genetics
  • Larva / immunology
  • Mesocestoides / chemistry*
  • Mesocestoides / genetics
  • Mesocestoides / immunology
  • Mice
  • Mice, Inbred BALB C
  • Proteomics

Substances

  • Helminth Proteins