3 years ago

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

Julia Fahel, Padraic G. Fallon, Antonio Alcami, Sean P. Saunders, Adnan R. Khan, Achilleas Floudas, Sylvie Amu, Christopher D. Cluxton
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.

Publisher URL: http://journals.plos.org/plosntds/article

DOI: 10.1371/journal.pntd.0006012

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