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Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

Abstract

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways.

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  • Authors+Show Affiliations

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.

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    Division of Emergency Medicine, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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    Division of Emergency Medicine, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.

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    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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    Division of Infectious Diseases, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

    Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: wherry@pennmedicine.upenn.edu.

    Source

    Cell reports 22:2 2018 Jan 09 pg 411-426

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29320737