title: Trained immunity in newborn infants of HBV-infected mothers.
abstract: 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.
authors: 1] 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.
authors: Michelle
authors: M
authors: Hong
authors: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors: Elena
authors: E
authors: Sandalova
authors: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
authors: Diana
authors: D
authors: Low
authors: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors: Adam J
authors: AJ
authors: Gehring
authors: UOC Ostetricia e Ginecologia, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
authors: Stefania
authors: S
authors: Fieni
authors: UO Immunoematologia e Medicina Trasfusionale, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
authors: Barbara
authors: B
authors: Amadei
authors: UO Immunoematologia e Medicina Trasfusionale, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
authors: Simonetta
authors: S
authors: Urbani
authors: 1] Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore [2] Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 1E Kent Ridge Road, Singapore 119228, Singapore.
authors: Yap-Seng
authors: YS
authors: Chong
authors: 1] Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore [2] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Block MD 7, 8 Medical Drive, Singapore 117597, Singapore.
authors: Ernesto
authors: E
authors: Guccione
authors: 1] 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 [3] School of Immunity and Infection, College of Medical and Dental Science, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Antonio
authors: A
authors: Bertoletti
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D066298:In Vitro Techniques; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053582:Interleukin-1alpha / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C508609:IL10 protein, human; C508584:IL1A protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10