Dynamics of Plasmodium berghei NK-65 parasitaemia and CD3+CD4+CD25+Fox-p3+ T-regulatory cells in experimentally induced malaria during early, mid, and late-pregnancy in BALB/c mice.

Abstract

Malaria in pregnancy causes a dual brunt on the mother as well as the foetus. Upregulation of T-regulatory cells (Tregs) during pregnancy allows tolerance towards the growing foetus, their suppression predisposes the mother to infections. This study analyzed the levels of CD3+CD4+CD25+Fox-p3+ Tregs, parasitaemia, maternal and foetal outcomes in BALB/c mice infected with P. berghei NK65 during early-, mid-, and late-pregnancy. Total of 114 mice, non-pregnant non-infected (n = 6), non-pregnant infected (n = 12), pregnant non-infected (n = 48) and pregnant infected (n = 48) were included in the study. Infected groups were inoculated intra-peritoneally with 1 × 106 P. berghei infected RBCs during early-, mid-, and late- pregnancy (D6, D10, and D14 respectively). Six mice from each stage were sacrificed on the 5th and 7th day post-infection (DPI) to evaluate parasitaemia (staining) and Tregs from splenocytes (by flow cytometry). The parasitaemia was significantly higher among early pregnancy infected mice (≥ 70%) than mid-pregnancy infected (40-70%), late pregnancy infected (50-65%), and non-pregnant infected mice (≤ 50%) (p < 0.05). The level of Tregs was significantly higher among non-pregnant infected mice as compared to non-pregnant non-infected mice (%Tregs 0.86 vs. 0.44). Among pregnant mice, the levels of Tregs in infected mice were lower than in non-infected mice during all stages of pregnancy. None of the mice infected during early- and mid-pregnancy survived at 6DPI and 7DPI, respectively, and those infected during late-pregnancy delivered premature pups. In contrast to non-pregnant mice, the levels of Tregs among pregnant mice decrease when malaria infection is acquired thereby leading to adverse pregnancy outcomes. The online version contains supplementary material available at 10.1007/s12088-023-01089-2.