Immune Gene Profiling in Healthy and HBV-exposed Cord Blood Immune Cells

The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a  potentially symbiotic relationship between HBV and its natural host and highlight the plasticity of the fetal immune system following viral exposure in utero. RNA was extracted from 15 cord blood samples comprising of healthy cord blood monocytes (n=4), HBV-exposed cord blood monocytes (n=3), healthy cord blood plasmacytoid dendritic cells (n=4), and HBV-exposed cord blood plasmacytoid dendritic cells (n=4). Healthy adult peripheral blood monocytes (n=3) were included for comparison. The immune profile was analyzed using Nanostring and nCounter® GX Human Immunology Kit v1, comprising probes for a total of 511 immune genes.