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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
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Trained immunity in newborn infants of HBV-infected mothers

Michelle Hong1, Elena Sandalova2, Diana Low3

  • 11] Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore [2] Emerging Infectious Diseases (EID) Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.

Nature Communications
|March 26, 2015
PubMed

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.

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