Immunological reactions in response to apicomplexan glycosylphosphatidylinositols

Apicomplexan protozoa are a phylum of parasites that includes pathogens such as Plasmodium, the causative agent of the most severe form of malaria responsible for almost 1 million deaths per year and Toxoplasma gondii causing toxoplasmosis, a disease leading to cerebral meningitis in immunocompromised individuals or to abortion in farm animals or in women that are infected for the first time during pregnancy. The initial immune reactions developed by the host are similar in response to an infection with Plasmodium and Toxoplasma in the sense that the same cells of the innate immune system are stimulated to produce inflammatory cytokines. The glycosylphosphatidylinositol (GPI) anchor is the major carbohydrate modification in parasite proteins and the GPIs are essential for parasite survival. Two immediate GPI precursors with the structures ethanolamine phosphate-6(Manalpha1-2)Manalpha1-2Manalpha1-6Manalpha1-4GlcN-PI and ethanolamine phosphate-6Manalpha1-2Manalpha1-6Man-alpha1-4-GlcN-PI are synthesized by P. falciparum. Two main structures are synthesized by T. gondii: ethanolamine phosphate-6Manalpha1-2Manalpha1-6(GalNAcbeta1-4)Manalpha1-4GlcN-PI and ethanolamine phosphate-6Manalpha1-2Manalpha1-6(Glcalpha1-4GalNAcbeta1-4)Manalpha1-4GlcN-PI. This review describes the biosynthesis of the apicomplexan GPIs and their role in the activation of the host immune system.