Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs)

摘要

Sm16 is a low molecular weight protein (~16kDa) secreted by Schistosoma mansoni, a causative agent of human schistosomiasis. The molecule is secreted by the infectious cercariae during skin invasion and performs an immune-suppressive function to protect the invading parasite from immune attack. Using phylogenetic and gene structure analysis we show that Sm16 homologues of parasites belonging to the Schistosomatoidea superfamily of digenean worms are members of the helminth defence molecule (HDM) family that are potent immune-modulators and exclusive to trematode species. Structural analyses revealed that Sm16, much like other HDMs, consists predominantly of an amphipathic alpha-helix. Sm16 is highly expressed in the cercariae and eggs of S. mansoni but not male or female adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. A synthetic form of the molecule, termed Sm16 (34 117), was shown to bind to and enter immune cells (macrophages) and induce a weak pro-inflammatory response. However, this peptide also blocked the pro-inflammatory effects of bacterial endotoxin (lipopolysaccharide, LPS). Analysis of the transcriptome of Sm16 (34 117)-stimulated macrophages in the presence or absence of LPS suggests that it mediates immunomodulatory activity via signalling pathways that are intricately involved in regulating cellular metabolism (fatty acid, cholesterol and glucose homeostasis) and central to inflammatory responses. These new insights into the structure and function of a well-known immunomodulatory molecule, Sm16, places it within a wider family of trematode-specific small molecule HDM immune-modulators with immuno-biotherapeutic possibilities.