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Impaired Cellular Immune Responses During the First Week of Severe Acute Influenza Infection


Abstract

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 of 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 ELISPOT assays.

Results

We recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three subjects required mechanical ventilation. Influenza-specific CD8+ T cell responses expanded prior to 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 to healthy controls. Inflammatory monocytes were significantly reduced in the three 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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