Severe Influenza Is Characterized by Prolonged Immune Activation: Results From the SHIVERS Cohort Study.

Sook-San Wong; Oshansky, Christine M.; Guo, Xi-Zhi J.; Ralston, Jacqui; Wood, Timothy; Seeds, Ruth; Newbern, Claire; Waite, Ben; Reynolds, Gary; Widdowson, Marc-Alain; Sue Huang, Q.; Webby, Richard J.; Thomas, Paul G.; Wong, Sook-San; Huang, Q Sue; 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.

INFLUENZA; CELLULAR immunity; IMMUNE response; INFECTION; SEVERITY of illness index; CYTOKINE genetics; IMMUNOLOGY; COMPARATIVE studies; CYTOKINES; DENDRITIC cells; IMMUNITY; INFLAMMATION; LONGITUDINAL method; LYMPHOCYTES; RESEARCH methodology; MEDICAL cooperation; MONOCYTES; RESEARCH; EVALUATION research

Journal of Infectious Diseases, 2018, Vol 217, Issue 2, p245

0022-1899

Academic Journal

10.1093/infdis/jix571