Abstract

BackgroundDuring childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. However, susceptibility to infection reappears in pregnant women, particularly primigravidae. This is due to appearance of antigenic parasite variants that are restricted to pregnancy. Variant-specific immunity also governs pregnancy-associated recrudescence of Plasmodium berghei infection in pregnant mice. Pregnancy-related changes in the plasma cytokine levels of mice with immunity acquired prior to first pregnancy have not been studied in detail previously, and were the topic of the present study.MethodsA multiplexed bead assay was used to measure plasma levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF in BALB/c mice immunized against P. berghei K173 by repeated infection and drug cure before the first pregnancy. The association between cytokine levels on the one hand and parasitaemia and haemoglobin levels on the other, in mice that had never been pregnant or were pregnant for the first, second or third time were evaluated by Mann–Whitney test and Spearman rank-order correlation analysis.ResultsPregnancy per se did not further increase the already high cytokine levels in mice previously immunized by repeated infection and drug cure. Levels of all the cytokines except IL-10 were correlated with each other, and with parasitaemia and haemoglobin levels. Furthermore, levels of all cytokines were positively correlated with parity, except IL-10, which was negatively correlated with parity. High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome.ConclusionsHigh levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome in this mouse model of placental malaria. Since the model replicates key parasitological and immunological features of placental P. falciparum malaria, it underpins its usefulness in immunology and pathogenesis studies of this important cause of mother/child morbidity in endemic areas.

Highlights

  • During childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults rarely experience clinical disease episodes

  • The impact of immunization and pregnancy on cytokine levels Plasmodium berghei infections in BALB/c mice cause a marked increase in plasma levels of many cytokines, including those measured in the present study

  • Immunization by repeated infection and sub-curative treatment led to high levels of IL-5, IL-10, IL-12, IL-13, Interferon- γ (IFN-γ), and Tumour necrosis factor (TNF) compared to uninfected mice, where levels were very low or undetectable

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Summary

Introduction

Residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults rarely experience clinical disease episodes. Several authors have shown that the mouse model developed in the 1980s by Eling and collaborators to study the impact of pregnancy on immunity to P. berghei infection [13,14,15], shares many immunological and pathogenic aspects with placental malaria in women [16,17]. On this basis, cytokine responses in this model and their relation to pregnancy outcome were investigated

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