Innate immune responses to malaria-infected erythrocytes in pregnant women: Effects of gravidity, malaria infection, and geographic location.

Marzieh Jabbarzare,Alexandra J Umbers,Wina Hasang,Stephen J Rogerson,Madi Njie,Maria Ome-Kaius,Anthony Jaworowski,Louise M Randall,Bill Kalionis

doi:10.1371/journal.pone.0236375

Abstract

BackgroundMalaria in pregnancy causes maternal, fetal and neonatal morbidity and mortality, and maternal innate immune responses are implicated in pathogenesis of these complications. The effects of malaria exposure and obstetric and demographic factors on the early maternal immune response are poorly understood.MethodsPeripheral blood mononuclear cell responses to Plasmodium falciparum-infected erythrocytes and phytohemagglutinin were compared between pregnant women from Papua New Guinea (malaria-exposed) with and without current malaria infection and from Australia (unexposed). Elicited levels of inflammatory cytokines at 48 h and 24 h (interferon γ, IFN-γ only) and the cellular sources of IFN-γ were analysed.ResultsAmong Papua New Guinean women, microscopic malaria at enrolment did not alter peripheral blood mononuclear cell responses. Compared to samples from Australia, cells from Papua New Guinean women secreted more inflammatory cytokines tumor necrosis factor-α, interleukin 1β, interleukin 6 and IFN-γ; p<0.001 for all assays, and more natural killer cells produced IFN-γ in response to infected erythrocytes and phytohemagglutinin. In both populations, cytokine responses were not affected by gravidity, except that in the Papua New Guinean cohort multigravid women had higher IFN-γ secretion at 24 h (p = 0.029) and an increased proportion of IFN-γ+ Vδ2 γδ T cells (p = 0.003). Cytokine levels elicited by a pregnancy malaria-specific CSA binding parasite line, CS2, were broadly similar to those elicited by CD36-binding line P6A1.ConclusionsGeographic location and, to some extent, gravidity influence maternal innate immunity to malaria.

Highlights

Malaria in pregnancy is responsible for 10,000 maternal deaths annually [1] and is associated with increased risk of miscarriage, stillbirth, fetal growth restriction, preterm deliveries, low birth weight (LBW) and infant mortality [2,3,4,5]
Peripheral blood mononuclear cell responses to Plasmodium falciparum-infected erythrocytes and phytohemagglutinin were compared between pregnant women from Papua New Guinea with and without current malaria infection and from Australia
Cytokine responses were not affected by gravidity, except that in the Papua New Guinean cohort multigravid women had higher interferon γ (IFN-γ) secretion at 24 h (p = 0.029) and an increased proportion of IFN-γ+ Vδ2 γδ T cells (p = 0.003)

Summary

Introduction

Malaria in pregnancy is responsible for 10,000 maternal deaths annually [1] and is associated with increased risk of miscarriage, stillbirth, fetal growth restriction, preterm deliveries, low birth weight (LBW) and infant mortality [2,3,4,5] These complications are associated with placental malaria, characterized by the attachment of Plasmodium falciparum-infected erythrocytes (IE) to chondroitin sulfate A (CSA) expressed on the placental syncytiotrophoblast. In contrast adults, including pregnant women, living in high and stable transmission areas acquire a substantial level of immunity and generally experience asymptomatic infections or mild malaria symptoms [4] They generally have previous exposure to a wide variety of PfEMP1 variants, which mediate adhesion to endothelial receptors such as CD36, intercellular adhesion molecule 1 and endothelial protein C receptor. The effects of malaria exposure and obstetric and demographic factors on the early maternal immune response are poorly understood.

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Discussion

Conclusion