SNPs at the IL-2, IL-12, TNF-α and TGF-β1 regulatory gene regions are probably important for Toxoplasma gondii congenital transmission and disease severity in humans.

Abstract

Toxoplasma gondii infection in pregnant females can cause congenital toxoplasmosis. Although maternal and infant immune profiles appear to play a role, studies on this topic are scarce. We analyzed SNPs in the regulatory regions of cytokine genes in 30 mother-newborn pairs, five mothers and two infants with known status, with respect to vertical transmission and the clinical outcome of those infected. Polymorphisms in the IL-2, IL-10, IL-12, IL-17, TNF-α, and TGF-β1 gene promoter or regulatory regions were obtained by sequencing, and genotype and allele frequencies were related to transmission and clinical outcome of the offspring. In children, the polymorphic "G" TNF-α -308 allele, as well as the related low- and high-level homozygous GG or TT genotypes of the 3'UTR region of the IL-12reg gene, were associated with congenital infection. Both cytokines have been shown to be expressed in the cyto- and syncytiotrophoblast; therefore, the fetus might be able to regulate infection at the placental level. In mothers of infected children, the T allele of the IL-12reg 3'UTR gene was associated with more severe disease in their offspring, suggesting that a strong maternal response reduces parasite spread in the fetus. Furthermore, SNPs in the promoter region of IL-2 and TGF-β1 genes were associated with elevated levels and milder disease in children with congenital infection, which is congruent with a regulation of a strong, damaging, inflammatory response. Our results suggest that some up and down regulatory cytokine genes may predispose to vertical transmission or disease severity in congenital toxoplasmosis.