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

• Published in: PLoS neglected tropical diseases 2017-10, Vol.11 (10), p.e0006012-e0006012
• Main Authors: Floudas, Achilleas, Cluxton, Christopher D, Fahel, Julia, Khan, Adnan R, Saunders, Sean P, Amu, Sylvie, Alcami, Antonio, Fallon, Padraic G
• Format: Article
• Language: English
• Subjects: Animals; Antigen-presenting cells; Antigens; Binding sites; Biology and Life Sciences; Bone marrow; CD4 antigen; Cell adhesion & migration; Cell proliferation; Cells; Composition; Cyclophilin; Cyclophilin A - genetics; Cyclophilin A - immunology; Dendritic cells; Dendritic Cells - immunology; Disease control; Female; Helminth Proteins - genetics; Helminth Proteins - immunology; Human blood fluke; Immune system; Immunity; Immunomodulation; Infections; Inflammation; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Male; Males; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Molecules; Parasites; Parasitic diseases; Proliferation; Protein composition; Protein Transport; Proteins; Recombinants; Research and Analysis Methods; Risk factors; Schistosoma mansoni; Schistosoma mansoni - genetics; Schistosoma mansoni - immunology; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - parasitology; Secretome; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - immunology; Tropical diseases; Vaccines
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006012

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.