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Severe influenza is characterized by prolonged immune activation: results from the SHIVERS cohort study

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  • Severe influenza is characterized by prolonged immune activation: results from the SHIVERS cohort study

    J Infect Dis. 2017 Nov 3. doi: 10.1093/infdis/jix571. [Epub ahead of print]
    Severe influenza is characterized by prolonged immune activation: results from the SHIVERS cohort study.

    Wong SS1, Oshansky CM2,3, Guo XJ2,4, Ralston J5, Wood T5, Reynolds G6, Seeds R5, Newbern C5, Waite B5, Widdowson MA3, Huang QS5, Webby RJ1, Thomas PG2,4; SHIVERS Investigation Team.
    Author information

    Abstract

    Background:

    The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of non-hospitalized individuals with influenza-like illness (ILI).
    Methods:

    Peripheral blood lymphocytes were collected from ILI (N=27) and SARI-patients (N=27) at time of enrollment and then two weeks later. Innate and adaptive cellular immune responses were assessed by flow-cytometry and serum cytokines were assessed by bead-based assay.
    Results:

    During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza-specific CD8+ and CD4+ T-cells compared to ILI. By convalescence however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza-specific, CD8+ T -cells compared to ILI. SARI was also associated with, reduced amounts of cytokines that regulate T-cell responses (IL4, IL13, IL12, IL10, TNFβ) and hematopoiesis (IL3, GM-CSF) but increased amounts of a pro-inflammatory cytokine (TNFα), chemotactic cytokines (MDC, MCP1, GRO, Fractalkine) and growth-promoting cytokines (PDGFBB/AA, VEGF, EGF) compared to ILI.
    Conclusions:

    Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation compared to mild influenza.


    KEYWORDS:

    cellular immunity; cytokine; disease severity; infection; influenza

    PMID: 29112724 DOI: 10.1093/infdis/jix571
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