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Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load
Christine M Oshansky, Andrew J Gartland, Sook-San Wong, Trushar Jeevan, David Wang, Philippa L Roddam, Miguela A Caniza, Tomer Hertz, John P DeVincenzo, Richard J Webby, and Paul G Thomas
+ Author Information.
Corresponding Author: Paul G Thomas, Email: Paul.Thomas@STJUDE.ORG
Abstract
Rationale: Children are an at-risk population for developing complications following influenza infection, but immunological correlates of disease severity are not understood. We hypothesized that innate cellular immune responses at the site of infection would correlate with disease outcome. Objectives: To test the immunological basis of severe illness during natural influenza virus infection of children and adults at the site of infection. Methods: 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. Measurements and Main Results: We show for the first time that while 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. Adjusting for age and viral load, an innate immune profile characterized by increased nasal lavage MCP-3, IFNα2 and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, MCP-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. Conclusions: An innate profile was identified that correlated with disease progression independent of viral dynamics and age. The airways and blood displayed dramatically different immune profiles emphasizing the importance of cellular migration and localized immune phenotypes.
KEYWORDS: natural influenza virus infection , monocyte, innate immune response, cytokine, human
Accepted December 5, 2013
Received September 9, 2013
Christine M Oshansky, Andrew J Gartland, Sook-San Wong, Trushar Jeevan, David Wang, Philippa L Roddam, Miguela A Caniza, Tomer Hertz, John P DeVincenzo, Richard J Webby, and Paul G Thomas
+ Author Information.
Corresponding Author: Paul G Thomas, Email: Paul.Thomas@STJUDE.ORG
Abstract
Rationale: Children are an at-risk population for developing complications following influenza infection, but immunological correlates of disease severity are not understood. We hypothesized that innate cellular immune responses at the site of infection would correlate with disease outcome. Objectives: To test the immunological basis of severe illness during natural influenza virus infection of children and adults at the site of infection. Methods: 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. Measurements and Main Results: We show for the first time that while 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. Adjusting for age and viral load, an innate immune profile characterized by increased nasal lavage MCP-3, IFNα2 and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, MCP-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. Conclusions: An innate profile was identified that correlated with disease progression independent of viral dynamics and age. The airways and blood displayed dramatically different immune profiles emphasizing the importance of cellular migration and localized immune phenotypes.
KEYWORDS: natural influenza virus infection , monocyte, innate immune response, cytokine, human
Accepted December 5, 2013
Received September 9, 2013
