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

Loyane Bertagnolli Coutinho; Mário Cézar de Oliveira; Ester Cristina Borges Araujo; Flávia Batista Ferreira França; Marcos Paulo Oliveira Almeida; Yusmaris Cariaco; Paulo Czarnewski; Neide Maria Silva

doi:10.1016/j.actatropica.2023.107022

Both C57BL/KsJ (H2^d haplotype) and CB10-H2 (H2^b haplotype) mice are highly susceptible to congenital toxoplasmosis

Acta Trop. 2023 Dec:248:107022. doi: 10.1016/j.actatropica.2023.107022. Epub 2023 Sep 15.

Authors

Loyane Bertagnolli Coutinho¹, Mário Cézar de Oliveira¹, Ester Cristina Borges Araujo¹, Flávia Batista Ferreira França¹, Marcos Paulo Oliveira Almeida¹, Yusmaris Cariaco¹, Paulo Czarnewski², Neide Maria Silva³

Affiliations

¹ Laboratory of Immunopathology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.
² Laboratory of Immunopathology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil; Present address: Science for Life Laboratory, Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Stockholm University, Solna, Sweden.
³ Laboratory of Immunopathology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil. Electronic address: nmsilva@ufu.br.

PMID: 37716667
DOI: 10.1016/j.actatropica.2023.107022

Abstract

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 (H2^d) were more resistant to congenital toxoplasmosis than C57BL/6 mice (H2^b). 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 H2^d -congenic C57BL/6 mice (C57BL/KsJ-H2^d) and H2^b-congenic BALB/c mice (CB10-H2-H2^b). 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 (H2^d) and CB10-H2 (H2^b) 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 pregnancy outcome in this mouse lineage.

Keywords: C57BL/KsJ; CB10-H2; Congenic mice; Congenital toxoplasmosis; Pregnancy outcome.

MeSH terms

Animals
Disease Susceptibility
Female
Haplotypes
Histocompatibility
Humans
Interleukin-6 / genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Pregnancy
Toxoplasma* / genetics
Toxoplasmosis, Animal* / parasitology
Toxoplasmosis, Congenital* / genetics

Substances

Interleukin-6