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

Details

• Alternative Title:
  J Infect Dis
• Personal Author:
  Wong, Sook-San ; Oshansky, Christine M. ; Guo, Xi-Zhi J. ; Ralston, Jacqui ; Wood, Timothy ; Seeds, Ruth ; Newbern, Claire ; Waite, Ben ; Reynolds, Gary ; Widdowson, Marc-Alain ; Huang, Q. Sue ; Webby, Richard J. ; Thomas, Paul G.
• Corporate Authors:
  SHIVERS Investigation Team
• Description:
  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.
  
  
• Subjects:
  Adaptive Immunity Adolescent Adult Aged Child Cohort Studies Cytokines Dendritic Cells Female Humans Immunity, Cellular Immunity, Innate Inflammation Influenza, Human Lymphocytes Male Middle Aged Monocytes Young Adult

  More +
• Keywords:
  Cellular Immunity Cytokine Disease Severity Infection Influenza
• Source:
  J Infect Dis. 217(2):245-256
• Pubmed ID:
  29112724
• Pubmed Central ID:
  PMC7335675
• Document Type:
  Journal Article
• Funding:
  U01 IP000480/IP/NCIRD CDC HHSUnited States/
• Volume:
  217
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:f11f7faac48db661a38e4fc9ba2f99824a251f672f44d7d3b7bc6b2aa9b99e15bb9c85e723dc703b4586a7c61cd4cdc5354192df9fa532f7a11edf420342dbb2
• Download URL:
  https://stacks.cdc.gov/view/cdc/90278/cdc_90278_DS1.pdf
• File Type:
  [PDF - 1.85 MB ]