Potential pharmacologic interventions targeting TLR signaling in placental malaria

• Published in: Trends in parasitology 2022-07, Vol.38 (7), p.513-524
• Main Authors: Kobia, Francis M., Maiti, Kaushik, Obimbo, Moses M., Smith, Roger, Gitaka, Jesse
• Format: Article
• Language: English
• Subjects: Female; fetal–maternal immune conflict; fetus; Humans; Infant, Newborn; innate immune responses; innate immunity; low birth weight; Malaria; Malaria, Falciparum; parasitology; pathogenesis; Placenta; placental malaria; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic - drug therapy; pregnancy outcomes
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2022.04.002

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. 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.