RT Journal Article T1 Virulence in Mice of a Toxoplasma gondii Type II Isolate Does Not Correlate With the Outcome of Experimental Infection in Pregnant Sheep A1 Sánchez Sánchez, Roberto A1 Ferré Pérez, Ignacio A1 Regidor Cerrillo, Javier A1 Gutiérrez Expósito, Daniel A1 Ferrer, Luis Miguel A1 Arteche Villasol, Noive A1 Moreno Gonzalo, Javier A1 Müller, Joachim A1 Aguado Martínez, Adriana A1 Pérez, Valentín A1 Hemphill, Andrew A1 Ortega Mora, Luis Miguel A1 Benavides, Julio AB Toxoplasma gondii is an apicomplexan parasite that infects almost all warm-blooded animals. Little is known about how the parasite virulence in mice extrapolates to other relevant hosts. In the current study, in vitro phenotype and in vivo behavior in mice and sheep of a type II T. gondii isolate (TgShSp1) were compared with the reference type II T. gondii isolate (TgME49). The results of in vitro assays and the intraperitoneal inoculation of tachyzoites in mice indicated an enhanced virulence for the laboratory isolate, TgME49, compared to the recently obtained TgShSp1 isolate. TgShSp1 proliferated at a slower rate and had delayed lysis plaque formation compared to TgME49, but it formed more cyst-like structures in vitro. No mortality was observed in adult mice after infection with 1-105 tachyzoites intraperitoneally or with 25-2,000 oocysts orally of TgShSp1. In sheep orally challenged with oocysts, TgME49 infection resulted in sporadically higher rectal temperatures and higher parasite load in cotyledons from ewes that gave birth and brain tissues of the respective lambs, but no differences between these two isolates were found on fetal/lamb mortality or lesions and number of T. gondii-positive lambs. The congenital infection after challenge at mid-pregnancy with TgShSp1, measured as offspring mortality and vertical transmission, was different depending on the challenged host. In mice, mortality in 50% of the pups was observed when a dam was challenged with a high oocyst dose (500 TgShSp1 oocysts), whereas in sheep infected with the same dose of oocysts, mortality occurred in all fetuses. Likewise, mortality of 9 and 27% of the pups was observed in mice after infection with 100 and 25 TgShSp1 oocysts, respectively, while in sheep, infection with 50 and 10 TgShSp1 oocysts triggered mortality in 68 and 66% of the fetuses/lambs. Differences in vertical transmission in the surviving offspring were only found with the lower oocyst doses (100% after infection with 10 TgShSp1 oocysts in sheep and only 37% in mice after infection with 25 TgShSp1 oocysts). In conclusion, virulence in mice of T. gondii type II isolates may not be a good indicator to predict the outcome of infection in pregnant sheep. PB Frontiers SN 2235-2988 YR 2019 FD 2019-01-04 LK https://hdl.handle.net/20.500.14352/112078 UL https://hdl.handle.net/20.500.14352/112078 LA eng NO Sánchez-Sánchez, R., Ferre, I., Regidor-Cerrillo, J., Gutiérrez-Expósito, D., Ferrer, L. M., Arteche-Villasol, N., Moreno-Gonzalo, J., Müller, J., Aguado-Martínez, A., Pérez, V., Hemphill, A., Ortega-Mora, L. M., & Benavides, J. (2019). Virulence in Mice of a Toxoplasma gondii Type II Isolate Does Not Correlate With the Outcome of Experimental Infection in Pregnant Sheep. Frontiers in Cellular and Infection Microbiology, 9(JAN). https://doi.org/10.3389/FCIMB.2018.00436 NO Author Contributions: IF, JR-C, VP, AH, LO-M, and JB conceived the study and participated in its design. LO-M coordinated the isolation, in vitro and mouse studies, and JB and LO-M coordinated the studies in sheep. RS-S, LO-M, and JB wrote the manuscript, with result interpretation and discussion inputs from IF, JR-C, and AH. JR-C, JM-G, and JB carried out the isolation of TgShSp1. RS-S and JR-C carried out in vitro experiments. LF selected sheep and executed the reproductive program. RS-S, IF, JR-C, and JM prepared tachyzoites or oocysts and performed the infections. RS-S, DG-E, NA-V, JM-G, AA-M, VP, and JB participated in inoculation and clinical examination of animals, performed necropsies and sampling of the animals and performed histopathological analyses. RS-S performed PCR and qPCR analyses, serological assays, and statistical analysis and interpreted the results. All authors read and approved the final manuscript. NO Ministerio de Educación y Formación Profesional (España) NO Ministerio de Universidades (España) NO European Commission NO Ministerio de Economía, Comercio y Empresa (España) NO Comunidad de Madrid NO Junta de Castilla y León NO Swiss National Science Foundation DS Docta Complutense RD 19 abr 2025