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Article: Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load

TitleMucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load
Authors
KeywordsCytokine
Human
Innate immune response
Monocyte
Natural influenza virus infection
Issue Date2014
Citation
American Journal of Respiratory and Critical Care Medicine, 2014, v. 189, n. 4, p. 449-462 How to Cite?
AbstractRationale: 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: Anobservational 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-a2, 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. © 2014 by the American Thoracic Society.
Persistent Identifierhttp://hdl.handle.net/10722/311963
ISSN
2023 Impact Factor: 19.3
2023 SCImago Journal Rankings: 5.336
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorOshansky, Christine M.-
dc.contributor.authorGartland, Andrew J.-
dc.contributor.authorWong, Sook San-
dc.contributor.authorJeevan, Trushar-
dc.contributor.authorWang, David-
dc.contributor.authorRoddam, Philippa L.-
dc.contributor.authorCaniza, Miguela A.-
dc.contributor.authorHertz, Tomer-
dc.contributor.authorDeVincenzo, John P.-
dc.contributor.authorWebby, Richard J.-
dc.contributor.authorThomas, Paul G.-
dc.date.accessioned2022-04-06T04:31:52Z-
dc.date.available2022-04-06T04:31:52Z-
dc.date.issued2014-
dc.identifier.citationAmerican Journal of Respiratory and Critical Care Medicine, 2014, v. 189, n. 4, p. 449-462-
dc.identifier.issn1073-449X-
dc.identifier.urihttp://hdl.handle.net/10722/311963-
dc.description.abstractRationale: 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: Anobservational 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-a2, 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. © 2014 by the American Thoracic Society.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Respiratory and Critical Care Medicine-
dc.subjectCytokine-
dc.subjectHuman-
dc.subjectInnate immune response-
dc.subjectMonocyte-
dc.subjectNatural influenza virus infection-
dc.titleMucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1164/rccm.201309-1616OC-
dc.identifier.pmid24308446-
dc.identifier.scopuseid_2-s2.0-84894231691-
dc.identifier.volume189-
dc.identifier.issue4-
dc.identifier.spage449-
dc.identifier.epage462-
dc.identifier.eissn1535-4970-
dc.identifier.isiWOS:000331792100015-

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