Leah Cabo - Boyle Lab
"Developmental disruption in the transplacental transmission strategy of Toxoplasma gondii"
Pregnancy is a unique and critical point of biological vulnerability to pathogens. Infection of a pregnant person with Toxoplasma gondii can result in transmission of the parasite to the developing fetus, often leading to considerable birth defects. Fetal infection requires the parasite to cross the maternal-fetal barrier, a junction primarily mediated by the placenta. The strategy by which T. gondii surmounts this architecturally intricate tissue barrier is poorly understood at both the cellular and molecular level. Critical to this process are placental trophoblasts, cells that undergo coordinated development into distinct differentiated subtypes (most notably progenitor cytotrophoblasts, CYTs; syncytiotrophoblasts, SYNs; and extravillous trophoblasts; EVTs) to form the most intimate point of association between maternal and fetal tissue. Data have shown these trophoblast types are differentially susceptible to T. gondii infection, indicating a previously underestimated level of complexity in the transplacental path of this parasite. Trophoblasts that do get infected, particularly CYTs which replenish all other trophoblast types, are vulnerable to sweeping host cell changes that are characteristic of T. gondii infection. Using a newly derived bipotent stem cell system, this work tests the hypothesis that T. gondii infection of CYTs alters their developmental trajectory to promote parasite infection in a manner that disrupts proper placental and fetal development. Transcriptomic, morphological, and functional data suggest that T. gondii-infected CYTs bear gene expression signatures that are more similar to infection-permissive mesenchymal EVTs than infection-resistant fused epithelial SYNs. These data suggest that T. gondii infection alters cell fate to favor one lineage at the cost of the other, potentially revealing a mechanism by which the parasite propagates its own survival and transmission.
Friday, October 22nd, 2021
A219B Langley Hall
12:00 PM