Abstract
BackgroundThe impact of placental malaria (PM) infection on the expression profile of some cytokines known to regulate T cell differentiation and function and their influence on birth weight remain unclear. Moreover, there are no reports showing the relationship between PM and IL-27 or IL-28A. This study therefore sought to investigate whether placental P. falciparum infection alters the expression profile of the cytokines IL-28A, IL-27, IL-17E and IL-6 in mothers and their new born.MethodsIn a cross-sectional study conducted between 2013 and 2015 in Yaoundé, Cameroon, peripheral, placental and cord blood samples were collected from 108 women at delivery. Parasitaemia was determined microscopically and haemoglobin levels determined using a Coulter counter. Plasma levels of cytokines (IL-28A, IL-27, IL-17E and IL-6) were measured by Luminex magnetic screening assay.ResultsMalaria parasite density in placenta impression smear associated negatively with maternal haemoglobin level (P < 0.0001) and baby birth weight (P = 0.016). While IL-17E, IL-27 and IL-28A levels were significantly higher in placental and cord plasma than in peripheral (P < 0.0001, < 0.001 and P = 0.026, respectively), an opposite relationship was observed with IL-6 (P = 0.0018). Multivariate analysis confirmed results of univariate analysis where the presence of malaria parasites or pigments in placenta tissue impression smears correlated with decrease levels of maternal IL-17E, IL-27 and IL-28A and neonate levels of IL-28A and IL-17E (0.0001 ≤ P ≤ 0.02). Placental and peripheral parasitaemias also correlated positively with peripheral plasma levels of IL-6 (rs = 0.18, P = 0.05 and rs = 0.17, P = 0.07, respectively). In addition, high maternal haemoglobin level associated with increasing levels of IL-17E, IL-27 and IL-28A in peripheral plasma (0.002 ≤ P ≤ 0.018) and high placental and cord plasma levels of these cytokines associated with increasing birth weight (0.0001 ≤ P ≤ 0.0027).ConclusionsPlacental malaria downregulates maternal plasma levels of IL-17E, IL-27 and IL-28A and neonates’ plasma levels of IL-17E and IL-28A cytokines, which could help for parasite clearance and increase child birth weight. The study is expected to provide leads that should help identify potential biomarkers for improved birth weight and therapeutic interventions.
Highlights
The impact of placental malaria (PM) infection on the expression profile of some cytokines known to regulate T cell differentiation and function and their influence on birth weight remain unclear
There was no significant difference in median age between P. falciparum-infected and non-infected women (P = 0.2)
There was no significant difference in the levels of IL-17E and IL28A between placental and cord plasma, IL-27 and IL-6 levels were significantly higher in placental plasma than in cord plasma (P = 0.0010 and P < 0.001, respectively). These results suggest that IL-17E, IL-27 and IL-28A are synthesized in the placenta with IL-28A and IL-17E crossing the placenta barrier, leading to their observed high levels in cord blood
Summary
The impact of placental malaria (PM) infection on the expression profile of some cytokines known to regulate T cell differentiation and function and their influence on birth weight remain unclear. Plasmodium-infected erythrocytes (IEs) accumulate in the placenta [1, 2], inducing attraction of some leucocytes in the organ, pathological changes that alter the materno-fetal exchange system and result into intra-uterine growth retardation and low birth weight [3]. It alters cytokine expression profile [4,5,6,7]. As regards IL-28A, previous studies presented this cytokine as a newly designated type III interferon (IFN)-λ, having antiviral effects [22, 23] and produced principally by antigen-presenting cells (APCs) [24]. IL-6, IL-27, IL17E, and IL-28A are critical cytokines possibly involved in the regulation of human immunological diseases induced by Th1, Th2, Treg, and Th-17 cells response imbalance [26]
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