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Title

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

AuthorsFloudas, Achilleas; Cluxton Christopher D.; Fahel, Julia; Khan, Adnan r.; Saunders, Sean P.; Amu, Sylvie; Alcamí, Antonio ; Fallon, Padraic G.
Issue Date26-Oct-2017
PublisherPublic Library of Science
CitationPLoS Neglected Tropical Diseases 11 (2017)
AbstractThe 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 CD4T 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.
URIhttp://hdl.handle.net/10261/165331
Identifiersdoi: 10.1371/journal.pntd.0006012
issn: 1935-2735
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