Role of innate immunity in pregnancy

Abstract

Preeclampsia is a hypertensive condition of pregnancy, in which multiple systems are affected. The syncytiotrophoblast of the placenta releases extracellular vesicles from 12 weeks all the way till term (40 weeks). Extracellular vesicles are comprised of microvesicles (STBMV) and exosomes (STBEX) which are responsible for carrying signals from the syncytiotrophoblast to the mother. The hypothesis is that STBMV and STBEX express complement biomarkers capable of activating the maternal complement system. Activated complement system may be implicated in the elevated blood pressure that characterises preeclampsia. Another hypothesis is that Hofbauer Cells (HFC) contribute to the surfactant concentration in the maternal blood during pregnancy. HFC are responsible for placental development, placental vasculogenesis and angiogenesis, however, it is still not established whether they play any protective role during pregnancy. HFC are similar as M1 phenotype macrophages and may protect the placenta and fetus during infection, like a typical macrophage. Isolation and characterization of STBEV were performed by using a modified dual-lobe placental perfusion system. Phenotyping of STBMV was achieved by flow-cytometry, and STBEX was phenotyped by using nanoparticle tracking analysis (NTA). Additional assessment of the phenotypes STBEV was performed by SDS-PAGE and Western blotting analysis. Complement proteins are a large group of proteins mainly produced by the liver. Complement proteins protect the body against pathogens via a cascade of events where classical, alternative and lectin pathway or either one of the pathway is activated. The complement system is mediated or controlled by soluble factor H (FH). Factor H like protein 5 (FHR5) is immunologically and structurally similar to FH and is a part of FH family of proteins. This study concluded that STBMV and the placenta syncytiotrophoblast and HFC express FHR5. This indicates that FHR5 may play a role in complement activation or downregulation during pregnancy and may cause preeclampsia. Further study is paramount to understand the role of FHR5 in pregnancy. This study also found the presence of SP-A and SP-D in HFC indicate that they play a crucial role during parturition. They may release collectin during partition to the mother to initiate the process of parturition. That is why is it paramount that further investigation should be carried out to fully understand the context of collectins in relation with HFC. Presence of Factor H in Hofbauer cells indicates that HFC may play a crucial role during implantation and tissue remodelling via complement mediation. The presence of FH in HFC has previously not been reported and their presence open a new field of study. The role of HFC during pregnancy is also not fully known which make it crucial for further study to be conducted.