Both C57BL/KsJ (H2d haplotype) and CB10-H2 (H2b haplotype) mice are highly susceptible to congenital toxoplasmosis

Infection with T. gondii is a significant health problem for pregnant women and a primary infection with this parasite during human pregnancy can cause congenital toxoplasmosis that may cause abortion, neonatal death, miscarriage, stillbirth or fetal abnormalities (Tenter et al., 2000). The clinical manifestations due to infection depend on the gestational age that primary maternal infection occurs, being that the rates of vertical transmission increase proportionally as the pregnancy progress, estimated in 17 % for the first and 65 % for the third trimesters, but the gestational complications occur inversely, with mild or asymptomatic consequences to the offspring at the third trimester, and severe fetal outcomes at the first trimester (reviewed by Borges et al., 2019).

The immune response during T. gondii infection is characterized by a T helper type 1 (Th1) response with tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-12 production (Sasai et al., 2018). During pregnancy, CD4⁺ T cells differentiate into different subsets and the adequate balance between them is crucial for an efficacious gestation (Wang et al., 2020). The success of pregnancy is accompanied by Th1 immunity during the peri‑implantation period to promote tissue remodeling and angiogenesis; thus, the response changes toward Th2-type cytokines, and at the time of parturition, Th1 immunity appears again to prepare for labor and delivery (Wang et al., 2020). Excessive production of IFN-γ, however, is associated with the pathogenesis of recurrent spontaneous abortions (Lash et al., 2006) and TNF is reported to be potentially deleterious for conception (Viganò et al., 2001). Maternal regulatory T cells (Tregs) expand during pregnancy and appear to prevent maternal rejection of the fetus in mice and human, since pregnancy fails in the absence of these cells (Aluvihare et al., 2004; Sasaki et al., 2004).

In T. gondii infection, genes from different regions of the host genome have been implicated in resistance to the infection. The MHC alleles function as important determinants of resistance or susceptibility to infection, and are also involved in the control of cyst numbers and encephalitis at later stages of infection, both in mice and humans (McLeod et al., 1989; Brown et al., 1994, 1995). In oral infection with T. gondii, the intestinal lesions that are observed in C57BL/6 mice were associated more with the genetic background of mice than with the MHC haplotype (Resende et al., 2008). Regarding congenital infection, our previous study demonstrated that C57BL/6 mice (H2^b haplotype) presented worse pregnancy outcomes compared to BALB/c mice (H2^d haplotype) (Coutinho et al., 2012; Sousa et al., 2021).

The relationship between the genetic variation of MHC class I and congenital toxoplasmosis have been poorly investigated. In the present study, pregnancy outcome under T. gondii infection was evaluated in the lineages of H2^d-congenic C57BL/6 mice (C57BL/KsJ-H2^d) and H2^b-congenic BALB/c mice (CB10-H2-H2^b).