The pregnancy-associated secretome in malaria pathogenesis and immunity during gestation

In pregnancy, fetal health, growth and development are dependent on normal placental development. However, the mechanisms that support maternal immune tolerance for the fetus, fetal nourishment, and pregnancy maintenance to term are not fully understood. Placental secretions into the intervillous space play a key role in shaping early placental function. In their entirety, they represent the pregnancy-associated secretome (PAS). PAS alterations have been associated with various complications such as fetal growth restriction, maternal anemia, and preterm birth. Placental malaria (PM), caused by the sequestration of Plasmodium falciparum -infected erythrocytes in the intervillous space, affects PAS composition. In this review, we explore how P. falciparum -induced changes of PAS may contribute to pathogenesis and immune dysregulation during pregnancy, as well as the possibilities of leveraging PAS components as biomarkers for the prevention, diagnosis, and management of PM.