Pathways deployed by human placental trophoblasts to confer viral resistance

During pregnancy, the placenta plays a vital role in protecting the developing fetus from microbial infections. The multinucleated and terminally differentiated syncytiotrophoblasts actively coordinate host defense through a multitude of mechanisms. In addition to forming a cellular barrier, the syncytiotrophoblasts release extracellular vesicles containing microRNAs from the chromosome 19 microRNA cluster (C19MC). These vesicle-packaged miRNAs, upon uptake by recipient cells, induce autophagy and limit viral infection, acting against a diverse panel of both DNA and RNA viruses. We have shown that medium conditioned by primary human trophoblast (PHT) cells, which contain these vesicles, confers resistance from pathogens associated with congenital infections to recipient non-placental cells. Furthermore, we have demonstrated that primary human trophoblasts constitutively produce interferon lambda 1 (IFNλ1), leading to a robust induction of interferon stimulated genes in an autocrine and paracrine manner. These parallel pathways, actively coordinated by PHT cells, contribute to the barrier function of the placenta, protecting the developing fetus from viral infections