Researchers at Leiden University have identified a schistosome lipid that seems to interact with the innate immune system through a Toll-like receptor (TLR). Interestingly, rather than promoting T-cell activation, this interaction induces the development of T cells with immunosuppressive potential.
Schistosomes are parasitic worms that chronically infect more than 200 million people in developing countries. Owing to complex interactions between the host immune system and the parasite — the product of a long period of co-evolution — the schistosomes can survive for many years.
In recent years, lipids have emerged as important modulators of the innate immune system. So, van der Kleij and colleagues set out to investigate the effects of schistosome lipids on the host immune response. Lipids from Schistosoma mansoni were fractionated using an ion-exchange column and then tested for their capacity to induce cytokine production.
A fraction containing phosphatidylserine was found to affect the maturation of dendritic cells (DCs) such that they induced the development of T cells secreting the immunosuppressive cytokine interleukin-10 (IL-10) in vitro. In co-culture, these T cells suppressed the proliferation of autologous T cells, an effect that was blocked by IL-10-specific antibodies. This effect seems to be specific for phosphatidylserine, as other schistosome extracts failed to induce the production of IL-10 by T cells in vitro. Mammalian phosphatidylserine had no effect on DC maturation.
Members of the TLR family have been shown to recognize other pathogen-associated lipids, and so they were candidates receptors for interaction with the schistosome phosphatidyl fraction. Antibodies specific for TLR2 blocked the induction of IL-10-secreting T cells by phosphatidylserine in vitro, indicating that TLR2 might be involved in the recognition of schistosome phosphatidylserine. Phospholipase digestion of the phosphatidylserine lipid fraction reduced its TLR2-stimulating capacity, confirming that the active moiety is a phosphatidylserine and not a contaminant. Further fractionation of the worm phosphatidylserine by HPLC pinpointed the TLR2-activating and IL-10-promoting activity to a lyso-phosphatidylserine fraction.
So, schistosome lyso-phosphatidylserine seems to signal through TLR2 to direct the induction of IL-10-secreting helper T cells, which might account for the skewing to IL-10 production and T-cell hyporesposiveness that is seen during chronic schistosomiasis.
ORIGINAL RESEARCH PAPER
Van Der Kleij, D. et al. A novel host–parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J. Biol. Chem. 277, 48122–48129 (2002)
Pearce, E. J. & MacDonald, A. S. The immunobiology of schistosomiasis. Nature Rev. Immunol. 2, 499–511 (2002)