Predicting clinical outcomes of influenza infection

Children are an at-risk population for developing complications following influenza infection, but immunologic correlates of disease severity are not understood. We hypothesize that innate cellular immune responses at the site of infection would correlate with disease outcome. To test this, we profiled the innate and adaptive immune responses following influenza infection in an observational cohort study with longitudinal sampling of peripheral and mucosal sites in 84 naturally influenza-infected individuals, including infants. Cellular responses, viral loads, and cytokines were quantified from nasal lavages and blood, and correlated to clinical severity.

 

We found that although viral loads in children and adults were similar, innate responses in the airways were stronger in children and varied considerably between plasma and site of infection. Moreover, an innate immune profile characterized by increased nasal lavage MCP-3, IFN-a2, and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, MCRP-3, and IL-6 levels predicted hospitalization. This inflammatory cytokine production correlated significantly with monocyte localization from the blood to the site of infection, with conventional monocytes positively correlating with inflammation. Increased frequencies of CD14lo monocytes were in the airways of participants with lower inflammatory cytokine levels. 

 

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Site-of-infection immune responses predict clinical outcomes. Correlation coefficients were determined for 741 pairs of cytokines within the nasal lavage or plasma. The heat map indicates the correlation coefficients, with red, green, and black indicating perfect positive, negative, and no correlation, respectively. Correlations with false discovery rate (FDR)-adjusted q value . 0.2 were set to zero 

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