Effects of Ovine Monocyte-Derived Macrophage Infection by Recently Isolated Toxoplasma gondii Strains Showing Different Phenotypic Traits

Simple Summary Toxoplasmosis is a zoonotic disease caused by a protozoan parasite called Toxoplasma gondii. This parasite affects all warm-blooded animals. It is one of the more common causes of abortions in sheep, which threatens both the welfare of the animals and the economic sustainability of the farms. The virulence of different T. gondii isolates have been studied in mice and humans, but little information is available regarding sheep. The aim of this work was to study how the genetic variability of six T. gondii strains, that were recently isolated from Spanish sheep, affected different phenotypic traits in an in vitro model using ovine monocyte-derived macrophages. Our results showed that the type III isolates had a higher internalization/infection rate than type II isolates. Moreover, these two isolates also were shown to have higher increments in cytokines that favored inflammation and a Th1 immune response. The results of this study differ with earlier findings in mouse models and in vitro investigations, as well as from results between the same genotypes and different genotypes; proving that more phenotypic traits are needed for the study of the virulence of T. gondii isolates. Ovine toxoplasmosis is one the most relevant reproductive diseases in sheep. The genetic variability among different Toxoplasma gondii isolates is known to be related to different degrees of virulence in mice and humans, but little is known regarding its potential effects in sheep. The aim of this study was to investigate the effect of genetic variability (types II (ToxoDB #1 and #3) and III (#2)) of six recently isolated strains that showed different phenotypic traits both in a normalized mouse model and in ovine trophoblasts, in ovine monocyte-derived macrophages and the subsequent transcript expression of cytokines and iNOS (inducible nitric oxide synthase). The type III isolate (TgShSp24) showed the highest rate of internalization, followed by the type II clonal isolate (TgShSp2), while the type II PRU isolates (TgShSp1, TgShSp3, TgShSp11 and TgShSp16) showed the lowest rates. The type II PRU strains, isolated from abortions, exhibited higher levels of anti-inflammatory cytokines and iNOS than those obtained from the myocardium of chronically infected sheep (type II PRU strains and type III), which had higher levels of pro-inflammatory cytokines. The present results show the existence of significant intra- and inter-genotypic differences in the parasite-macrophage relationship that need to be confirmed in in vivo experiments.