Potential pharmacologic interventions targeting TLR signaling in placental malaria

In P. falciparum malaria endemic regions, expectant women are at high risk of placental malaria due to P. falciparum sequestration in the placenta, which adversely affects pregnancy outcomes. Placental malaria persists even when the peripheral parasite has been cleared from maternal circulation or is undetectable, and is detectable only by placental histological analysis. There are no interventions for clearing P. falciparum from the placenta or reversing associated placental injury. Poor placental malaria outcomes are attributed to maternal innate immune reactions to P. falciparum sequestration in the placenta. Studies show that fetal innate immune responses counter maternal responses, improving placental malaria outcomes. Evidence suggests that pharmacologically targeting fetal–maternal innate immune interactions during placental malaria may improve pregnancy outcomes. Complications from placental malaria cause poor pregnancy outcomes, including low birthweight, preterm delivery, and stillbirths. Many of these complications are driven by maternal innate proinflammatory responses to the sequestration of Plasmodium falciparum in the placenta. However, recent studies show that, in reaction to maternal innate immune responses that are detrimental to the fetus, the fetus mounts innate immune counter-responses that ameliorate pregnancy outcomes. Such fetal–maternal conflict in placental malaria has potential for pharmacologic modulation for better pregnancy outcomes. Here, we discuss placental malaria pathogenesis, its complications, and the role of innate immunity and fetal–maternal innate immune conflict in placental malaria. Finally, we discuss pharmacologic immunomodulatory strategies and agents with the potential to improve placental malaria outcomes. Complications from placental malaria cause poor pregnancy outcomes, including low birthweight, preterm delivery, and stillbirths. Many of these complications are driven by maternal innate proinflammatory responses to the sequestration of Plasmodium falciparum in the placenta. However, recent studies show that, in reaction to maternal innate immune responses that are detrimental to the fetus, the fetus mounts innate immune counter-responses that ameliorate pregnancy outcomes. Such fetal–maternal conflict in placental malaria has potential for pharmacologic modulation for better pregnancy outcomes. Here, we discuss placental malaria pathogenesis, its complications, and the role of innate immunity and fetal–maternal innate immune conflict in placental malaria. Finally, we discuss pharmacologic immunomodulatory strategies and agents with the potential to improve placental malaria outcomes. a temporary uterine tissue derived from the endometrium. It is made up of various cell types, including differentiated endometrial stromal cells, maternal vascular cells, and maternal blood cells. The decidua is critical for implantation and maintenance of pregnancy. in malaria-endemic regions, IPTp-SP is recommended for malaria prophylaxis in pregnant women and is offered during antenatal clinic visits. inflammation of the placental intervillous space. failure of fetal growth rate to reach its genetically determined growth potential. the World Health Organization defines low birthweight as a weight at birth of less than 2500 g (2.5 kg). women who have been pregnant at least two times. the World Health Organization defines preterm delivery as a live birth before 37 weeks of pregnancy are complete. Preterm delivery is further divided into (i) extremely preterm (born at <28 weeks of gestation), (ii) very preterm (born at between 28 and 32 weeks of gestation), and (iii) moderate–late preterm (born at between 32 and 37 weeks of gestation). women with a first-time pregnancy. as defined by the World Health Organization, the death of a fetus after 28 weeks of pregnancy but prior to, or during, delivery. However, the definition of stillbirth varies with individual countries. a layer of specialized epithelial cells covering the whole surface of villous trees. Syncytiotrophoblasts are in direct contact with the mother's blood.