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

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 m...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Achilleas Floudas, Christopher D Cluxton, Julia Fahel, Adnan R Khan, Sean P Saunders, Sylvie Amu, Antonio Alcami, Padraic G Fallon
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2017
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Online Access:https://doi.org/10.1371/journal.pntd.0006012
https://doaj.org/article/2caae958a3194774b15aabc3ecabf88b
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Summary: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.