Synthetic Plasmodium falciparum GPI: TLR recognition and structural requirements
Abstract number: R2455
Cramer J.P., Kamena F., Lepenies B., Liu X., Burchard G.D., Seeberger P.H., Jacobs T.
Plasmodium falciparum malaria is confined to blood stage parasites. Host immune response to parasite antigens is essential for parasite clearance but also contributes to disease manifestation. Plasmodial glycosylphosphatidylinositol (GPI) contributes to malaria pathology by induction of excessive cytokine release via Toll-like receptor (TLR) 2. Since GPI is a promising anti-disease vaccine candidate, identification of structural requirements for TLR-activation is relevant.
Applying synthetic P. falciparum GPI-glycan analogues we identified GPI moieties required for immune activation. On RAW264.7 macrophages, GPI substructures lacking the diacylglycerol moiety were still stimulatory. However, at least four mannose residues were required for TNF-alpha induction. Integration of lipidated GPI into erythrocyte membranes induced increased TNF-alpha and IL-12 compared to pure compound.
We conclude that the glycan moiety is the immune-stimulatory moiety while the acyl chains confer optimal presentation of the molecule on cell surfaces.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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