PA-773 Placental foetal-maternal innate immune responses to placental malaria

Abstract

Background During malaria in pregnancy (MiP), Plasmodium falciparum-infected erythrocytes sequester in the placenta, causing placental malaria (PM) and poor pregnancy outcomes, including low birthweight, preterm birth, and stillbirth. Mouse data indicate that innate immune response to PM on the placenta’s maternal side adversely affects the foetus and in response, the placenta’s foetal side mounts an innate counterresponse that improves foetal outcomes. However, this has not been observed in human PM.

Methods We used histological and molecular analyses to characterize the PM status of bio banked placentas and corresponding maternal sera. Molecular tools were used to characterize innate immune responses to human PM in the foetal and maternal sides of the placenta.

Results Histology and molecular assays showed that 50% of women who had no history of MiP and had received malaria chemoprophylaxis, had PM. Among women with MiP history, the PM rate was 70%. RT-qPCR revealed that foetal sides of PM-negative samples had lower levels of Toll-like receptor (TLR)- 4 and 9 when compared with maternal sides of the same placentas. However, in PM-positive placentas, their levels were higher in foetal sides than maternal sides of the same placentas. Moreover, TLR4 was significantly upregulated in maternal sides of PM-positive placentas versus maternal sides of PM-negative placentas. Intriguingly, TLR4 was significantly upregulated in foetal sides of PM-positive placentas versus foetal sides of PM-free placentas. Immunohistochemical analysis revealed that when compared with PM-negative tissue, PM-positive samples expressed markedly higher levels of 8-hydroxy-2’-deoxyguanosine, a marker of oxidative DNA damage. RT-qPCR showed that this was accompanied by the upregulation of p21, a marker of DNA damage repair.

Conclusion Our data indicate that human PM drives differential innate immune response in foetal vs maternal sides of the placenta, and triggers placental oxidative DNA damage. These observations may have implications for the diagnosis and management of PM.

https://doi.org/10.1136/bmjgh-2023-EDC.297