Abstract
BackgroundIncreased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. Peripheral and cord mononuclear cells were stimulated with Plasmodium falciparum lysate and secretion of IL-12p70, IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF, TNF-β was quantified in culture supernatants by multiplex flow cytometry while cellular mRNA expression of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10 and IL-13 was measured by quantitative PCR.ResultsHigher concentrations of IL-6 and IL-1β were associated with a reduced risk of P. falciparum infection in pregnant women (p < 0.049). Pro-inflammatory cytokines IL-6, IL-1β and TNF strongly correlated among themselves (ρ > 0.5, p < 0.001). Higher production of IL-1β was significantly associated with congenital malaria (p < 0.046) and excessive TNF was associated with peripheral infection and placental lesions (p < 0.044).ConclusionsComplex network of immuno-pathological cytokine mechanisms in the placental and utero environments showed a potential trade-off between positive and negative effects on mother and newborn susceptibility to infection.
Highlights
Increased susceptibility to malaria during pregnancy is not completely understood
Kinetics of cytokine and chemokine production by cells after Plasmodium falciparum antigen stimulation To determine the optimal timepoint for cytokine and chemokine secretion in supernatants after stimulation with infected red blood cells (iRBC) and uninfected red blood cells (uRBC) lysates, a pilot study was conducted with 44 maternal Peripheral blood mononuclear cells (PBMC) and 44 matched cord blood mononuclear cells (CBMC) samples (28 aparasitaemic and 16 parasitaemic mothers)
For some cytokines (IFN-γ, IL-6, IL-10, tumor necrosis factor (TNF)) responses tended to be higher at 24 h and this timepoint was chosen for subsequent studies
Summary
Increased susceptibility to malaria during pregnancy is not completely understood. Cellular immune responses mediate both pathology and immunity but the effector responses involved in these processes have not been fully characterized. Maternal and fetal cytokine and chemokine responses to malaria at delivery, and their association with pregnancy and childhood outcomes, were investigated in 174 samples from a mother and child cohort from Mozambique. The negative outcomes of Plasmodium falciparum infections on health concentrate in infants and pregnant women [1]. Cellular responses have been involved in pathology. Dobaño et al Malar J (2018) 17:177 falciparum induces placental immune responses involving TH1 and T H2 pathways [11] but increasing T H1/ pro-inflammatory responses involving IL-1β, IL-6, IL-8 and TNF to a greater extent. Production of IFN-γ by placental cells (natural killer and CD4+ TH1 cells) has been associated with protection against placental malaria [14,15,16,17]
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