Van der Kleij et al. investigated the interaction of schistosome-derived lipids with the immune system and showed that schistosomal phosphatidylserine (PS) activated Toll-like receptors (TLR) on human dendritic cells, causing the dendritic cells to promote the differentiation of T cells into the T regulatory (Treg) phenotype. The chronic stage of infection with schistosomes, parasitic trematodes that cause schistosomiasis, is characterized by enhanced production of interleukin-10 (IL-10) and suppression of the T cell response to parasite antigens. The authors determined that the PS fraction of lipids isolated from Schistosoma mansoni eggs and worms and fractionated on anion-exchange columns stimulated cytokine production in peripheral blood mononuclear cells from healthy individuals. When cocultured with naïve T cells, monocyte-derived dendritic cells that were matured in the presence of schistosomal PS promoted the development of IL-10 producing Treg cells that were capable of suppressing the proliferation of autologous T helper (TH) cells. In HEK 293 cells transiently transfected with various human TLRs, only cells carrying TLR-2 were activated by schistosomal PS. Maturing dendritic cells in the presence of antibodies to TLR-2 (as well as schistosomal PS) attenuated their ability to promote the differentiation of IL-10-producing T cells. The authors used mass spectrometry in combination with HPLC to identify lysophosphatidylserine as the TLR-2-stimulating molecule. Activity was specific to schistosomal-derived lysophosphatidylserine; neither mammalian PS nor synthetic lysophosphatidylserine were effective.
D. van der Kleij, E. Latz, J. F. H. M. Brouwers, Y. C. M. Kruize, M. Schmitz, E. A. Kurt-Jones, T. Espevik, E. C. de Jong, M. L. Kapsenberg, D. T. Golenbock, A. G. M. Tielens, M. Yazdanbakhsh, A novel host-parasite lipid cross-talk. J. Biol. Chem. 277, 48122-48129 (2002). [Abstract] [Full Text]