Composition of the Schistosoma mansoni worm secretome: Identification of immune modulatory Cyclophilin A

PLoS Negl Trop Dis. 2017 Oct 26;11(10):e0006012. doi: 10.1371/journal.pntd.0006012. eCollection 2017 Oct.

Abstract

The helminth Schistosoma mansoni modulates the infected host's immune system to facilitate its own survival, by producing excretory/secretory molecules that interact with a variety of the host's cell types including those of the immune system. Herein, we characterise the S. mansoni adult male worm secretome and identify 111 proteins, including 7 vaccine candidates and several molecules with potential immunomodulatory activity. Amongst the molecules present in the secretome, a 17-19kDa protein analogous to human cyclophilin A was identified. Given the ability of cyclophilin A to modulate the immune system by regulating antigen presenting cell activity, we sought to determine whether recombinant S. mansoni Cyclophilin A (rSmCypA) is capable of modulating bone-marrow derived dendritic cell (BMDC) and T cell responses under in vitro conditions. rSmCypA was enzymatically active and able to alter the pro-inflammatory cytokine profile of LPS-activated dendritic cells. rSmCypA also modulated DC function in the induction of CD4+ T cell proliferation with a preferential expansion of Treg cells. This work demonstrates the unique protein composition of the S. mansoni male worm secretome and immunomodulatory activity of S. mansoni Cyclophilin A.

MeSH terms

  • Animals
  • Cyclophilin A / genetics
  • Cyclophilin A / immunology*
  • Dendritic Cells / immunology
  • Female
  • Helminth Proteins / genetics
  • Helminth Proteins / immunology*
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Transport
  • Schistosoma mansoni / genetics
  • Schistosoma mansoni / immunology*
  • Schistosomiasis mansoni / immunology
  • Schistosomiasis mansoni / parasitology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Helminth Proteins
  • Cyclophilin A

Grant support

This work was supported by Science Foundation Ireland. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.