Understanding iron regulation of Toxoplasma gondii dissemination during acute infection

Arp, Allison

Publication

Understanding iron regulation of Toxoplasma gondii dissemination during acute infection

Arp, Allison

Description

Toxoplasma gondii (T. gondii) is a highly prevalent protozoan present in 30% of people world-wide. This parasite is a serious health threat to developing fetuses and immunocompromised individuals. To date, there are no therapies or vaccines which provide thorough, sterilizing immunity to T. gondii. Understanding mechanisms that promote the success of this pathogen are important to develop novel therapeutics. T. gondii infection is controlled by the host via IFNγ. IFNγ is known to mediate nutrient starvation of the parasite, and, in particular, to limit the availability of iron. Iron is a vital cofactor sequestered by the parasite from the host within infected cells. Based upon published results from in vitro studies, iron sequestration from the host is thought to be essential for parasite growth and replication. However, our preliminary data indicates that, as opposed to lack of growth in vitro, continuous limitation via iron chelation with deferiprone dramatically increased chronic infection burden in mice. These conflicting results render the importance of iron in parasite dissemination in vivo unclear. To clarify said importance, we treated mice with deferiprone and compared acute infection parasite burdens in the spleen, liver, small intestine, brain, and lungs after 7 days of infection with either ME49 or RH parasite strains. Real time PCR analysis was performed on extracted tissue DNA. Our results will, for the first time, define how iron availability impacts parasite dissemination in vivo and lead to a better understanding of the pathogenesis of this infection for more rational therapy design.