Mechanisms of placental dysfunction during Plasmodium falciparum infection in pregnancy

Placental malaria infection, during which infected red blood cells sequester in the placenta, is a substantial cause of pregnancy-related complications in areas where malaria is endemic. Accumulation of infected red blood cells creates an inflammatory environment and induces an immune response that can be deleterious to the placenta. This response can cause complications that include low birth weight, which is a major risk factor for neonatal and infant death. A decrease in the megalin transport and signaling system has been demonstrated to be linked with placental malaria infection and to be connected with low birth weight pathology. In this study we analyze the abundance of a protein related to megalin, LRP1 (LDL receptor related protein 1) in pregnancy malaria. Protein expression was analyzed in placental tissue samples by immunofluorescence staining. A statistically significant decrease was observed in the expression of LRP1 in placental samples of patients stratified by presence of placental malaria infection and infants born with low birth weight. Findings were supported using an in vitro cell model of placental syncytial trophoblast during malarial infection. In this model BeWo cell line was incubated with erythrocytes infected with malaria parasite CS2 line that is known for binding to malaria placental receptor. LRP1 expression in BeWo cells was analyzed by immunostaining and Western Blot, and a reduction was found by both methods. Analysis of LRP1 mRNA levels by RT-qPCR revealed no difference compared to control samples, indicating that changes happen at the protein level.