Abstract
BackgroundLiver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear.MethodsTo understand the pathogenesis of liver disease during malaria in pregnancy, comparative proteomic analysis of the liver in a mouse model of malaria in pregnancy was performed.ResultsDecreased levels of mitochondrial and peroxisomal proteins were observed in the livers of pregnant mice infected with the lethal rodent malaria parasite Plasmodium berghei strain NK65. By contrast, increased levels of perilipin-2, amyloid A-1, and interferon (IFN)-γ signalling pathway-related proteins were observed in the livers of infected pregnant mice, suggesting that IFN-γ signalling may contribute to the development of liver disease during malaria in pregnancy. IFN-γ signalling is a potential trigger of inducible nitric oxide synthase (iNOS) expression. Liver disease associated with microvesicular fatty infiltration and elevated liver enzymes in pregnant wild-type mice infected with malaria parasites was improved by iNOS deficiency.ConclusionsIn this study, a causative role of iNOS in liver disease associated with microvesicular fatty infiltration during malaria in pregnancy was demonstrated. These findings provide important insight for understanding the role of iNOS-mediated metabolic responses and the pathogenesis of high-risk liver diseases in pregnancy, such as acute fatty liver.
Highlights
Liver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear
Proteomic analysis of the liver of immunized pregnant mice infected with P. berghei NK65 Plasmodium berghei XAT is an attenuated parasite and C57BL/6 mice cured of P. berghei XAT infection have acquired protective immunity that suppresses the severe pathology caused by the lethal malaria parasite P. berghei NK65 [24]
Mice immunized with the attenuated parasite with or without a vaginal plug were secondarily infected with the lethal malaria parasite P. berghei NK65, as described previously [12] (Fig. 1A)
Summary
Liver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear. Malaria in Severe anaemia, thrombocytopenia, and liver dysfunction are common features of severe malaria [7]. These pathological features of pregnant women infected with Plasmodium falciparum can be confused with haemolytic anaemia, elevated liver enzymes, and low platelet count (HELLP) syndrome [8,9,10]. In North-western Colombia, hepatic dysfunction is the most frequent complication in patients with severe cases (9 of 15 patients) [11]. These findings indicate that hepatic dysfunction is common during human placental malaria
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