Cytokine response to pregnancy-associated recrudescence of Plasmodium berghei infection in mice with pre-existing immunity to malaria

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.

Role of some biomarkers in placental malaria in women living in Yaoundé, Cameroon

“…These observations corroborate previous findings in Africa where high plasma levels of IL-10 were associated with malaria infection during pregnancy (Kabyemela et al, 2008;Nmorsi et al, 2010;Boström et al, 2012;Chandrasiri Upeksha et al, 2013;Chêne et al, 2014). High IL-10 levels have also been reported in mice models during pregnancy malaria (Megnekou et al, 2013). Although no significant correlation was observed between CXCL-10 levels and parity, the level of this chemokine was high irrespective of gravidity.…”

Placental Cytokine and Chemokine Profiles Reflect Pregnancy Outcomes in Women Exposed to Plasmodium falciparum Infection

“…However, the suggestion from our data, as discussed above, of a suppressive effect of P. falciparum infection, reflected by the concentrations of different T cell-derived cytokines in placental plasma at delivery, requires further investigation in this context. There are striking similarities, furthermore, between our findings concerning cytokine concentrations and those of a recently published study using a murine model of placental malaria infection (34). This appears to strengthen the idea that infection-related suppression of T cell activity-regardless of whether it is the cause or the effect-may play a role in determining pregnancy outcomes.…”

Immunization of mice with soluble lysate of interferon gamma expressing Plasmodium berghei ANKA induces high IFN-γ production

“…The delayed parasitemia patency coupled with prolonged parasitemia suppression and survival time in the treatment groups may be due to the high IFN-γ and TNF-α levels present prior to challenge infection. This observation has been reported in previous studies where clearance of blood stage infection coincides with high IFN-γ levels [ 23 , 26 , 27 ]. Other studies have equally confirmed the involvement of TNF-α in Plasmodium clearance [ 24 ], [ 25 ].…”