Schistosomal lysophosphatidylserine: an immonumodulatory factor

Abstract

Schistosomes are parasitic worms that cause schistosomiasis, a chronic disease associated with a Th2 response. During the chronic phase of infection the disease is also associated with enhanced IL-10 production and suppressed T cell proliferation against parasite and third party antigens. The tegumental outer-surface structure of schistosomes is unique in nature and consists of a syncytium of fused cells covered by two closely-apposed lipid bilayers that form the interactive surface with the host. Schistosome-specific lysophosphatidylserine (lysoGPSer) activates toll-like receptor 2 (TLR2) and affects dendritic cells in such a way that mature dendritic cells gain the ability to induce the development of IL-10 producing regulatory T cells. We present a novel HPLC-MS/MS method that separates molecular species of all phospholipid classes in one single run. Using this method, more that 400 phospholipid species were identified and quantified in crude lipid extracts from Schistosoma mansoni. Furthermore, we analysed the phospholipid species composition of phosphatidylserine and lysophospholipids in adult worms, in isolated tegumental membranes of adult schistosomes and in blood cells of the host. It was shown that the tegument comprises many schistosome-specific and tegument-specific phospholipids. We also show that lysophosphatidylserine species with saturated acyl chains containing 16 to 20 carbon atoms have very poor activating capacity, while long chain lysophosphatidyl species (22 carbon atoms of longer) have a potent TLR2 activating capacity. Finally, we show the effect of schistosomal lipid fractions on the immune system of Gabonese children living in an area endemic for schistosomiasis. A lipid fraction contained lysophospahtidylserine (lysoGPSer) plus diacylphosphatidylserine (GPSer) while the other one contained lysoGPSer and only a trace of GPSer. The effect of the lipid fractions was compared with commercial available TLR2 ligands. LysoGPSer plus GPSer was shown to have different immunological effects compared to lysoGPser.