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 Devincenzo, Richard J. Webby, Paul G. Thomas

Research output: Contribution to journalArticle

62 Citations (Scopus)

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: 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.

Original languageEnglish (US)
Pages (from-to)449-462
Number of pages14
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume189
Issue number4
DOIs
StatePublished - Feb 15 2014

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Mucosal Immunity
Viral Load
Human Influenza
Chemokine CCL7
Nasal Lavage
Monocytes
Infection
Cytokines
Interleukin-10
Immunologic Tests
Immune System Diseases
Virus Diseases
Orthomyxoviridae
Innate Immunity
Cellular Immunity
Disease Progression
Interleukin-6
Hospitalization
Cohort Studies
Inflammation

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load. / Oshansky, Christine M.; Gartland, Andrew J.; Wong, Sook San; Jeevan, Trushar; Wang, David; Roddam, Philippa L.; Caniza, Miguela A.; Hertz, Tomer; Devincenzo, John; Webby, Richard J.; Thomas, Paul G.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 189, No. 4, 15.02.2014, p. 449-462.

Research output: Contribution to journalArticle

Oshansky, CM, Gartland, AJ, Wong, SS, Jeevan, T, Wang, D, Roddam, PL, Caniza, MA, Hertz, T, Devincenzo, J, Webby, RJ & Thomas, PG 2014, 'Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load', American Journal of Respiratory and Critical Care Medicine, vol. 189, no. 4, pp. 449-462. https://doi.org/10.1164/rccm.201309-1616OC
Oshansky, Christine M. ; Gartland, Andrew J. ; Wong, Sook San ; Jeevan, Trushar ; Wang, David ; Roddam, Philippa L. ; Caniza, Miguela A. ; Hertz, Tomer ; Devincenzo, John ; Webby, Richard J. ; Thomas, Paul G. / Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load. In: American Journal of Respiratory and Critical Care Medicine. 2014 ; Vol. 189, No. 4. pp. 449-462.
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