Toxoplasma gondii <i>GRA28</i> Is Required for Placenta-Specific Induction of the Regulatory Chemokine CCL22 in Human and Mouse
Elizabeth N. Rudzki, Stephanie E. Ander, Rachel S. Coombs, Hisham S. Alrubaye, Leah F. Cabo, Matthew L. Blank, Nicolás Gutiérrez-Melo, J. P. Dubey, Carolyn B. Coyne, Jon P. Boyle
Abstract
Toxoplasma gondii is a globally ubiquitous pathogen that can cause severe disease in HIV/AIDS patients and can also cross the placenta and infect the developing fetus. We have found that placental and immune cells infected with T. gondii secrete significant amounts of a chemokine (called CCL22) that is critical for immune tolerance during pregnancy. In order to better understand whether this is a response by the host or a process that is driven by the parasite, we have identified a T. gondii gene that is absolutely required to induce CCL22 production in human cells, indicating that CCL22 production is a process driven almost entirely by the parasite rather than the host. Consistent with its role in immune tolerance, we also found that T. gondii parasites lacking this gene are less able to proliferate and disseminate throughout the host. Taken together, these data illustrate a direct relationship between CCL22 levels in the infected host and a key parasite effector and provide an interesting example of how T. gondii can directly modulate host signaling pathways in order to facilitate its growth and dissemination.