Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiationReport as inadecuate




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Malaria Journal

, 15:497

First Online: 07 October 2016Received: 24 July 2016Accepted: 04 October 2016DOI: 10.1186-s12936-016-1545-6

Cite this article as: Prahl, M., Jagannathan, P., McIntyre, T.I. et al. Malar J 2016 15: 497. doi:10.1186-s12936-016-1545-6

Abstract

BackgroundIn malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses.

MethodsUsing cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes.

ResultsCord blood FoxP3 Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy 12–20 weeks of gestation; p = 0.048, but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery by loop-mediated isothermal amplification LAMP; p = 0.810. In contrast, higher frequencies of activated CD4 T cells CD25FoxP3CD127 were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery p = 0.035. This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria p < 0.0001.

ConclusionTogether, these data indicate that in utero exposure to malaria drives expansion of both regulatory and effector T cells in the fetus, and that the timing of this exposure has a pivotal role in determining the polarization of the fetal immune response.

KeywordsPregnancy-associated malaria Fetal immune response Immune tolerance CD4 T cells Dendritic cells Loop-mediated isothermal amplification  Download fulltext PDF



Author: Mary Prahl - Prasanna Jagannathan - Tara I. McIntyre - Ann Auma - Lila Farrington - Samuel Wamala - Mayimuna Nalubega - Ke

Source: https://link.springer.com/







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