Toxoplasma uses tough love

Parasites are known for outwitting their hosts in unexpected ways, and Toxoplasma gondii is no exception. To ensure that it does not kill its host prematurely, T. gondii secretes a protein that induces a strong host cellular immune response. This response slows the infection—and enables the parasite to complete its life cycle. Now, Julio Aliberti, Jesus Valenzuela, Alan Sher, and colleagues (NIH, Bethesda, MD) have identified the T. gondii protein that triggers the immune response and found that it mimics a chemokine.

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. ▪

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