Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation

Malaria Journal

Research

Pamela Odorizzi¹  Diane V. Havlir¹  Prasanna Jagannathan¹  Hilary Vance¹  Grant Dorsey¹  Tara I. McIntyre¹  Rachel Budker¹  Lila Farrington¹  Mary Prahl²  Margaret E. Feeney³  Abel Kakuru⁴  Mayimuna Nalubega⁴  Kate Naluwu⁴  Kenneth Musinguzi⁴  Samuel Wamala⁴  Ann Auma⁴  Patience Nayebare⁴  Esther Sikyoma⁴  John Ategeka⁴  Moses R. Kamya⁵ 

[1] Department of Medicine, University of California-San Francisco, 3333 California Street, Suite 315, 94143, San Francisco, CA, USA;Department of Pediatrics, University of California-San Francisco, Box 1234, 3333 California Street, Suite 315, 94143, San Francisco, CA, USA;Department of Pediatrics, University of California-San Francisco, Box 1234, 3333 California Street, Suite 315, 94143, San Francisco, CA, USA;Department of Medicine, University of California-San Francisco, 3333 California Street, Suite 315, 94143, San Francisco, CA, USA;Infectious Diseases Research Collaboration, PO Box 7475, 2C Nakasero Hill Road, Kampala, Uganda;School of Medicine, College of Health Sciences, Makerere University of College of Health Sciences, PO Box 7072, Kampala, Uganda;

关键词: Pregnancy-associated malaria;    Fetal immune response;    Immune tolerance;    CD4 T cells;    Dendritic cells;    Loop-mediated isothermal amplification;   

DOI  :  10.1186/s12936-016-1545-6

 received in 2016-07-24, accepted in 2016-10-04,  发布年份 2016

来源: Springer

【 摘 要 】

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 (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).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.

【 授权许可】

CC BY   
© The Author(s) 2016