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Nat Commun. 2015 Mar 25;6:6588. doi: 10.1038/ncomms7588.

Trained immunity in newborn infants of HBV-infected mothers.

Author information

1
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.
2
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
3
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
4
UOC Ostetricia e Ginecologia, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
5
UO Immunoematologia e Medicina Trasfusionale, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
6
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.
7
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.
8
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.

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.

PMID:
25807344
PMCID:
PMC4389241
DOI:
10.1038/ncomms7588
[Indexed for MEDLINE]
Free PMC Article

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