Toxoplasma Chinese 1 Strain of WH3Δ rop16 I/III / gra15 II Genetic Background Contributes to Abnormal Pregnant Outcomes in Murine Model

infection evokes a strong Th1-type response with interleukin (IL)-12 and interferon (IFN)-γ secretion. Recent studies suggest that the infection of pregnant mice with may lead to adverse pregnancy results caused by subversion of physiological immune tolerance at maternofetal interface rather than direct invasion of the parasite. Genotype-associated dense granule protein GRA15 tends to induce classically activated macrophage (M1) differentiation and subsequently activating NK, Th1, and Th17 cells whereas rhoptry protein ROP16 drives macrophages to alternatively activated macrophage (M2) polarization and elicits Th2 immune response. Unlike the archetypal strains of types I, II, and III, type Chinese 1 strains possess both GRA15 and ROP16 , suggesting a distinct pathogenesis of -involved adverse pregnancies. We constructed type Chinese 1 strain of WH3Δ based on CRISPR/Cas9 technology to explore the ROP16 -deficient/GRA15 -dominant parasites in induction of trophoblast apoptosis and abnormal pregnant outcomes of mice . Our study showed that WH3Δ remarkably induced apoptosis of trophoblasts. C57BL/6 pregnant mice injected with the tachyzoites of WH3Δ presented increased absorptivity of fetuses in comparison with the mice infected with WH3 wild type (WH3 WT) parasites although no remarkable difference of virulence to mice was seen between the two strains. Additionally, the mice inoculated with WH3Δ tachyzoites exhibited a notable expression of both IL-17A and IFN-γ, while the percentage of CD4 CD25 FoxP3 [T regulatory cells (Tregs)] were diminished in splenocytes and placenta tissues compared to those infected with WH3 WT parasites. Accordingly, expressions of IL-4, IL-10, and transforming growth factor beta 1, the pivotal cytokines of Th2 and Tregs response, were significantly dampened whereas IFN-γ and IL-12 expressions were upregulated in WH3Δ -infected mice, which gave rise to more prominent outcomes of abnormal pregnancies. Our results indicated that the WH3Δ parasites with background of type Chinese 1 strains may cause miscarriage and stillbirth due to subversion of the maternal immune tolerance and system immunity of the animals and the GRA15 effector contributes to the process of adverse pregnant consequences.