Schistosome secretomes.

Schistosomes are intravascular parasitic platyhelminths (blood flukes) that infect over 200 million people globally. Biomolecules secreted by the worms likely contribute to their ability to survive in the bloodstreams of immunocompetent hosts for many years. Here we review what is known about the protein composition of material released by the worms. Prominent among cercarial excretions/secretions (ES) is a ∼ 30 kDa serine protease called cercarial elastase (SmCE in Schistosoma mansoni), likely important in host invasion. Also prominent is a 117 amino acid non-glycosylated polypeptide (Sm16) that can impact several host cell-types to impinge on immunological outcomes. Similarly, components of the egg secretome (notably the 134 amino acid homodimeric glycoprotein "IL-4 inducing principle of schistosome eggs", IPSE, and the 225-amino acid monomeric T2 ribonuclease - omega-1) are capable of driving Th2-biased immune responses. A ∼36kDa chemokine binding glycoprotein SmCKBP, secreted by eggs, can negate the impact of several cytokines and can impede neutrophil migration. Of special interest is a disparate collection of classically cytosolic proteins that are surprisingly often identified in schistosome ES across life stages. These proteins, perhaps released as components of extracellular vesicles (EVs), include glycolytic enzymes, redox proteins, proteases and protease inhibitors, heat shock proteins, proteins involved in translation/turnover, histones, and others. Some such proteins may display "moonlighting" functions and, for example, impede blood clot formation around the worms. More prosaically, since several are particularly abundant soluble proteins, their appearance in the ES fraction may be indicative of worm damage ex vivo leading to protein leakage. Some bioactive schistosome ES proteins are in development as novel therapeutics against autoimmune, inflammatory, and other, non-parasitic, diseases.