Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation
Abstract Background In 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 comp...
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ftdoajarticles:oai:doaj.org/article:231777e8762e44aab12e86ef5d057122 2023-05-15T15:16:28+02:00 Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation Mary Prahl Prasanna Jagannathan Tara I. McIntyre Ann Auma Lila Farrington Samuel Wamala Mayimuna Nalubega Kenneth Musinguzi Kate Naluwu Esther Sikyoma Rachel Budker Hilary Vance Pamela Odorizzi Patience Nayebare John Ategeka Abel Kakuru Diane V. Havlir Moses R. Kamya Grant Dorsey Margaret E. Feeney 2016-10-01T00:00:00Z https://doi.org/10.1186/s12936-016-1545-6 https://doaj.org/article/231777e8762e44aab12e86ef5d057122 EN eng BMC http://link.springer.com/article/10.1186/s12936-016-1545-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-016-1545-6 1475-2875 https://doaj.org/article/231777e8762e44aab12e86ef5d057122 Malaria Journal, Vol 15, Iss 1, Pp 1-10 (2016) Pregnancy-associated malaria Fetal immune response Immune tolerance CD4 T cells Dendritic cells Loop-mediated isothermal amplification Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2016 ftdoajarticles https://doi.org/10.1186/s12936-016-1545-6 2022-12-31T12:44:30Z Abstract Background In 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. Methods Using 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. Results Cord 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 (CD25+FoxP3−CD127+) 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). Conclusion Together, 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 15 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Pregnancy-associated malaria Fetal immune response Immune tolerance CD4 T cells Dendritic cells Loop-mediated isothermal amplification Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Pregnancy-associated malaria Fetal immune response Immune tolerance CD4 T cells Dendritic cells Loop-mediated isothermal amplification Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Mary Prahl Prasanna Jagannathan Tara I. McIntyre Ann Auma Lila Farrington Samuel Wamala Mayimuna Nalubega Kenneth Musinguzi Kate Naluwu Esther Sikyoma Rachel Budker Hilary Vance Pamela Odorizzi Patience Nayebare John Ategeka Abel Kakuru Diane V. Havlir Moses R. Kamya Grant Dorsey Margaret E. Feeney Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation |
topic_facet |
Pregnancy-associated malaria Fetal immune response Immune tolerance CD4 T cells Dendritic cells Loop-mediated isothermal amplification Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background In 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. Methods Using 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. Results Cord 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 (CD25+FoxP3−CD127+) 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). Conclusion Together, 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. |
format |
Article in Journal/Newspaper |
author |
Mary Prahl Prasanna Jagannathan Tara I. McIntyre Ann Auma Lila Farrington Samuel Wamala Mayimuna Nalubega Kenneth Musinguzi Kate Naluwu Esther Sikyoma Rachel Budker Hilary Vance Pamela Odorizzi Patience Nayebare John Ategeka Abel Kakuru Diane V. Havlir Moses R. Kamya Grant Dorsey Margaret E. Feeney |
author_facet |
Mary Prahl Prasanna Jagannathan Tara I. McIntyre Ann Auma Lila Farrington Samuel Wamala Mayimuna Nalubega Kenneth Musinguzi Kate Naluwu Esther Sikyoma Rachel Budker Hilary Vance Pamela Odorizzi Patience Nayebare John Ategeka Abel Kakuru Diane V. Havlir Moses R. Kamya Grant Dorsey Margaret E. Feeney |
author_sort |
Mary Prahl |
title |
Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation |
title_short |
Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation |
title_full |
Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation |
title_fullStr |
Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation |
title_full_unstemmed |
Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation |
title_sort |
timing of in utero malaria exposure influences fetal cd4 t cell regulatory versus effector differentiation |
publisher |
BMC |
publishDate |
2016 |
url |
https://doi.org/10.1186/s12936-016-1545-6 https://doaj.org/article/231777e8762e44aab12e86ef5d057122 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 15, Iss 1, Pp 1-10 (2016) |
op_relation |
http://link.springer.com/article/10.1186/s12936-016-1545-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-016-1545-6 1475-2875 https://doaj.org/article/231777e8762e44aab12e86ef5d057122 |
op_doi |
https://doi.org/10.1186/s12936-016-1545-6 |
container_title |
Malaria Journal |
container_volume |
15 |
container_issue |
1 |
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1766346765770948608 |