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Severe influenza is characterized by prolonged immune activation: results from the SHIVERS Cohort Study

journal contribution
posted on 04.10.2019 by Sook-San Wong, Christine M. Oshansky, Xi-Zhi J. Guo, Jacqui Ralston, Tim Wood, Ruth Seeds, Elizabeth Claire Newbern, Ben Waite, Gary Reynolds, Marc-Alain Widdowson, Qiu Sue Huang, Richard J. Webby, Paul G. Thomas, SHIVERS Investigation Team
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 nonhospitalized individuals with influenza-like illness (ILI).

Methods. Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay.

Results. During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus–specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus–specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor β) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI.

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

Funding

Centers for Disease Control and Prevention (CDC)

Department of Health and Human Services (Cooperative agreement 1U01IP000480-01)

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