The T. gondii protein, cyclophillin-18 (C-18), binds to the CCR5 receptor on the surface of dendritic cells and induces the expression of high levels of IL-12, a positive regulator of cell-mediated immunity. The fact that C-18 works through a chemokine receptor is unusual. “In general this sort of [IL-12] induction has been thought of as working solely through Toll-like receptors,” says Sher.
Although C-18 alone is already a more effective IL-12 activator than other known triggers like CPG or LPS, the team has evidence that there is a second immune-stimulating factor produced by T. gondii that boosts the levels even further. This second factor appears to work via a Toll receptor, but the ligand has not yet been identified.
Although there is precedent for parasitic mimics of chemokine ligands, particularly in malaria, these proteins work to promote parasitic infection. C-18 is the first one identified that limits the parasitic infection. ▪