<i>Toxoplasma</i> effector GRA15-driven CCL5 secretion enhances brain parasite load through microvascular sequestration of phagocytes

The intracellular parasite <i>Toxoplasma gondii</i> invades immune cells to spread through the circulatory system, eventually reaching the brains of humans and animals. It is not well understood how parasitized immune cells interact with blood vessel walls, a process that ultimately helps <i>Toxoplasma</i> colonize the brain tissue. We found that when Toxoplasma infects the cells lining the blood vessels (endothelium), these produce C-C motif chemokine ligand 5 (CCL5), a potent signaling and attractant molecule. CCL5 production was triggered by a parasite-derived secreted protein, GRA15. CCL5 activated and attracted infected immune cells. In mice, the levels of CCL5 increased quickly in the brain microvasculature after infection, helping the infected immune cells adhere to brain vessels. When the effect of CCL5 was pharmacologically blocked, fewer infected cells sequestered in the brain vessels, lowering the parasite loads. These findings reveal a mechanism through which <i>Toxoplasma</i> manipulates host cells to produce factors that facilitate its colonization of the brain.