Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 222, Issue 7, Pages 1235-1244Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiaa226
Keywords
Influenza; cellular immunity; illness severity; CD8+T cell; B cell; monocyte
Categories
Funding
- Emergency Medicine Foundation
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR002345]
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Background. Cellular immune responses are not well characterized during the initial days of acute symptomatic influenza infection. Methods. We developed a prospective cohort of human subjects with confirmed influenza illness of varying severity who presented within a week after symptom onset. We characterized lymphocyte and monocyte populations as well as antigen-specific CD8(+) T-cell and B-cell responses from peripheral blood mononuclear cells using flow cytometry and enzyme-linked immunospot assays. Results. We recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three patients required mechanical ventilation. Influenza-specific CD8(+) T-cell responses expanded before the appearance of plasmablast B cells. However, the influenza-specific CD8(+) T-cell response was lower in infected subjects than responses seen in uninfected control subjects. Circulating populations of inflammatory monocytes were increased in most subjects compared with healthy controls. Inflammatory monocytes were significantly reduced in the 3 subjects requiring mechanical ventilation. Inflammatory monocytes were also reduced in a separate validation cohort of mechanically ventilated patients. Conclusions. Antigen-specific CD8(+) T cells respond early during acute influenza infection at magnitudes that are lower than responses seen in uninfected individuals. Circulating inflammatory monocytes increase during acute illness and low absolute numbers are associated with very severe disease.
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