Do the placental barrier, parasite genotype and Toll-like receptor polymorphisms contribute to the course of primary infection with various Toxoplasma gondii genotypes in pregnant women?

Abstract

Toxoplasma gondii has a highly clonal genetic structure classified into three major genetic types, I, II, and III, plus additional recombinant and atypical strains. In humans, type I and atypical strains usually associate with severe toxoplasmosis. Type II strains, predominantly identified in European countries and the United States, correlate with a differential course of toxoplasmosis. During pregnancy, the important protective role of the placenta against maternal–fetal T. gondii transmission has been reported. T. gondii preferentially colonizes extravillous trophoblasts as compared to syncytiotrophoblasts. The latter compartment was suggested to act as the real barrier to the fetal dissemination of T. gondii. Alterations in immune response to particular T. gondii strains were observed. Higher transcription levels of IP-10, IL-1β, IL-6, IL-10, IL-12 cytokines, and NF-κB translocation to the nucleus were more often documented for type II strains than type I strains. Since the induction of IL-12 during type II infection was Myd88-dependent, the involvement of Toll-like receptors (TLRs) in the immunity against these strains was suggested. Differential expression of TLRs depends on placental cell types and gestational age. The expression of TLR2 and TLR4 in the first trimester of pregnancy was reported only for villous cytotrophoblasts and extravillous trophoblasts, but not for syncytiotrophoblasts. The involvement of single-nucleotide polymorphisms (SNPs) in the TLR genes in infectious pathogenicity, including toxoplasmic retinochoroiditis, points at a possible involvement of TLR alterations in immunity against T. gondii. We conclude that studies on TLR contributions in the maternal–fetal transmission of particular parasite strains and congenital toxoplasmosis are warranted.