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

tetano

Editor, Senior Moderator
J Infect Dis. 2017 Nov 3. doi: 10.1093/infdis/jix571. [Epub ahead of print]
[h=1]Severe influenza is characterized by prolonged immune activation: results from the SHIVERS cohort study.[/h] Wong SS[SUP]1[/SUP], Oshansky CM[SUP]2,[/SUP][SUP]3[/SUP], Guo XJ[SUP]2,[/SUP][SUP]4[/SUP], Ralston J[SUP]5[/SUP], Wood T[SUP]5[/SUP], Reynolds G[SUP]6[/SUP], Seeds R[SUP]5[/SUP], Newbern C[SUP]5[/SUP], Waite B[SUP]5[/SUP], Widdowson MA[SUP]3[/SUP], Huang QS[SUP]5[/SUP], Webby RJ[SUP]1[/SUP], Thomas PG[SUP]2,[/SUP][SUP]4[/SUP]; SHIVERS Investigation Team.
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]Background:[/h] 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).
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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.
[h=4]Conclusions:[/h] Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation compared to mild influenza.


[h=4]KEYWORDS:[/h] cellular immunity; cytokine; disease severity; infection; influenza

PMID: 29112724 DOI: 10.1093/infdis/jix571
 
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