Innate Immune Mechanisms to Protect Against Infection at the Human Decidual-Placental Interface

Abstract

During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier resulting in pathogenic transmission from mother to fetus. Innate immune responses, orchestrated by maternal and fetal cells at the decidual-placental interface, are the first line of defense to avoid vertical transmission. Here, we outline the anatomy of the human placenta and uterine lining, the decidua, and discuss the potential capacity of pathogen pattern recognition and other host defense strategies present in the innate immune cells at the placental-decidual interface. We consider major congenital infections that access the placenta from hematogenous or decidual route. Finally, we highlight the challenges in studying human placental responses to pathogens and vertical transmission using current experimental models and identify gaps in knowledge that need to be addressed. We further propose novel experimental strategies to address such limitations.

Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms

“…Due to the Th1/Th2 dynamics and pregnancy-related physiological adaptations, such as an oedematous upper respiratory tract and diaphragm elevation [ 10 ], pregnant women are generally considered to be more susceptible to viral respiratory pathogens compared to non-pregnant women [ 11 ]. To protect the developing foetus, the placenta functions both as a physical as well as an immunological barrier between the maternal and foetal compartment [ 12 ]. However, the local immune tolerant environment, at the level of the placenta, allows for some susceptibility to viral replication and transplacental transmission, as has been shown with TORCH infections (toxoplasmosis, “other”, rubella, CMV and herpes simplex) [ 13 ] and more recently with the Zika virus [ 14 , 15 ].…”

The Role of Innate Immune System in the Human Amniotic Membrane and Human Amniotic Fluid in Protection Against Intra-Amniotic Infections and Inflammation

“…Neutrophils and monocytes/macrophages are most abundant in hAM in acute chorioamnionitis and natural killer cells can also be found, while CD3+ and CD8+ lymphocytes are present in moderate amounts in chronic chorioamnionitis with smaller number of CD4+ (helper T) cells (115-117, 141, 225-227). As is explained in the reviews by Cappelletti et al (80) and Hoo et al (227), during normal pregnancy, the decidual-placental interface is rich with immune cells, which become activated in IAI and migrate towards amnio-chorionic membrane (80). The immune cells involved in the inflammation are of maternal and fetal origin, and must maintain a delicate balance of eliminating an infection, while preventing the damage to the fetus.…”

“…Unsurprisingly, the immune cells are also present in amnio-chorionic membrane, and the presence (and abundance) of neutrophils or lymphocytes defines the stage of acute or chronic chorioamnionitis, respectively ( 116 , 117 ). Neutrophils and monocytes/macrophages are most abundant in hAM in acute chorioamnionitis and natural killer cells can also be found, while CD3+ and CD8+ lymphocytes are present in moderate amounts in chronic chorioamnionitis with smaller number of CD4+ (helper T) cells ( 115 – 117 , 141 , 225 – 227 ). As is explained in the reviews by Cappelletti et al.…”

“…( 80 ) and Hoo et al. ( 227 ), during normal pregnancy, the decidual-placental interface is rich with immune cells, which become activated in IAI and migrate towards amnio-chorionic membrane ( 80 ). The immune cells involved in the inflammation are of maternal and fetal origin, and must maintain a delicate balance of eliminating an infection, while preventing the damage to the fetus.…”

Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives

“…The primary mechanism of VZV transfer across the placenta remains unclear; however, it is postulated that T-cells infected with varicella virus bathe the decidua basalis, where the virus replicates and spreads into the intervillous space [ 87 ]. Both CD4 and CD8 T-cells are reprogrammed following VZV infection, rendering them more capable of crossing into the intervillous space [ 88 ].…”