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

• Published in: Acta tropica 2023-12, Vol.248, p.107022-107022, Article 107022
• Main Authors: Coutinho, Loyane Bertagnolli, de Oliveira, Mário Cézar, Araujo, Ester Cristina Borges, França, Flávia Batista Ferreira, Almeida, Marcos Paulo Oliveira, Cariaco, Yusmaris, Czarnewski, Paulo, Silva, Neide Maria
• Format: Article
• Language: English
• Subjects: C57BL/KsJ; CB10-H2; Congenic mice; Congenital toxoplasmosis; Pregnancy outcome
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2023.107022

•Both C57BL/KsJ (H2d) and CB10-H2 (H2b) mice showed adverse pregnancy outcomes.•C57BL/KsJ displayed worse pregnancy outcome than CB10-H2 mice in early gestation.•The adverse pregnancy outcomes were associated with high IFN-γ and TNF levels.•The adverse pregnancy outcome in C57BL/KsJ was also associated with high IL-6 levels.•Specific antibody responses were not protective against the poor pregnancy outcomes. Congenital toxoplasmosis may cause abortion, neonatal death, or foetal abnormalities. Despite little information from human studies, a genetic influence over congenital disease was demonstrated and, host genome have been implicated to resistance/susceptibility to Toxoplasma gondii infection in both human and mice. It was previously shown that BALB/c mice (H2d) were more resistant to congenital toxoplasmosis than C57BL/6 mice (H2b). However, it is unclear whether these differences are attributable to the MHC haplotype or to other components of the mouse's genetic background. Therefore, in this work, we intend to address this question by investigating the pregnancy outcome in H2d -congenic C57BL/6 mice (C57BL/KsJ-H2d) and H2b-congenic BALB/c mice (CB10-H2-H2b). For this, animals were infected by intragastric route on the first day of pregnancy and examined on days 8 (8dP/8dI) or 18 (18dP/18dI) of gestation and infection. The pregnancy outcome, parasite burden, systemic cytokine profile and antibody response to infection were evaluated. Infected mice showed adverse pregnancy outcomes, in parallel low parasite detection in the uterus/placenta, being that the C57BL/KsJ showed the worst results in relation to CB10-H2 mice. Both mouse lineages showed an increase in IFN-γ and TNF levels systemically on 8dP/8dI and on 18dP/18dI, and C57BL/KsJ showed an increase in IL-6 levels in both gestation/infection periods. Additionally, C57BL/KsJ showed 7- and 7-fold increase in IL-6, 4- and 2.5-fold increase in IFN-γ and, 6- and 4-fold increase in TNF production on 8dP/8dI and 18dP/18dI, respectively in association with 1.5-fold decrease in TGF-β levels on 8dP/8dI compared to CB10-H2 mice. In conclusion, the high IFN-γ and TNF serum levels observed in C57BL/KsJ (H2d) and CB10-H2 (H2b) mice were involved in the poor pregnancy outcomes in congenital toxoplasmosis. In addition, the higher IFN‐γ, IL‐6 and TNF levels detected in C57BL/KsJ in relation to CB10‐H2 mice on 8dP/8dI seem to be related to the genetic background of C57BL/6J mice that may have contributed to the worse