Innate Immune Responses To Malaria-Infected Erythrocytes In Pregnant Women: Effects Of Gravidity, Malaria Infection, And Geographic Location

Background Malaria 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. Methods Peripheral blood mononuclear cell responses toPlasmodium 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 gamma, IFN-gamma only) and the cellular sources of IFN-gamma were analysed. Results Among 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-alpha, interleukin 1 beta, interleukin 6 and IFN-gamma; p<0.001 for all assays, and more natural killer cells produced IFN-gamma 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-gamma secretion at 24 h (p = 0.029) and an increased proportion of IFN-gamma V+delta 2 gamma delta 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. Conclusions Geographic location and, to some extent, gravidity influence maternal innate immunity to malaria.