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Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load
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Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load
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Journal Article
Mucosal Immune Responses Predict Clinical Outcomes during Influenza Infection Independently of Age and Viral Load
2014
Overview
Abstract
Rationale
Children are an at-risk population for developing complications following influenza infection, but immunologic 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 immunologic 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 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. Adjusting for age and viral load, an innate immune profile characterized by increased nasal lavage monocyte chemotactic protein-3, IFN-α2, and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, monocyte chemotactic protein-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.
Publisher
Oxford University Press,American Thoracic Society
Subject
/ Adult
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Biological and medical sciences
/ Child
/ Female
/ Humans
/ Infant
/ Influenza, Human - diagnosis
/ Influenza, Human - immunology
/ Male
/ Nasal Lavage Fluid - immunology
/ Original
/ Respiratory Mucosa - immunology
/ Respiratory Mucosa - virology
/ Reverse Transcriptase Polymerase Chain Reaction
/ Viral diseases of the respiratory system and ent viral diseases
