Journal of Clinical Immunology

, Volume 30, Issue 3, pp 373–383

Influenza-Induced Production of Interferon-Alpha is Defective in Geriatric Individuals

Authors

  • David H. Canaday
    • Geriatric Research, Education and Clinical Center (GRECC)Cleveland VA Medical Center
    • Division of Infectious Diseases, Department of MedicineCase Western Reserve University
  • Naa Ayele Amponsah
    • Division of Infectious Diseases, Department of MedicineCase Western Reserve University
  • Leola Jones
    • Division of Infectious Diseases, Department of MedicineCase Western Reserve University
  • Daniel J. Tisch
    • Department of Epidemiology and BiostatisticsCase Western Reserve University
  • Thomas R. Hornick
    • Geriatric Research, Education and Clinical Center (GRECC)Cleveland VA Medical Center
    • Department of PathologyCase Western Reserve University
Article

DOI: 10.1007/s10875-010-9374-9

Cite this article as:
Canaday, D.H., Amponsah, N.A., Jones, L. et al. J Clin Immunol (2010) 30: 373. doi:10.1007/s10875-010-9374-9

Abstract

Background

The majority of deaths (90%) attributed to influenza are in person’s age 65 or older. Little is known about whether defects in innate immune responses in geriatric individuals contribute to their susceptibility to influenza.

Objective

Our aim was to analyze interferon-alpha (IFN-alpha) production in peripheral blood mononuclear cells (PBMCs) isolated from young and geriatric adult donors, stimulated with influenza A or Toll-like receptor (TLR) ligands. IFN-alpha is a signature anti-viral cytokine that also shapes humoral and cell-mediated immune responses.

Results

Geriatric PBMCs produced significantly less IFN-alpha in response to live or inactivated influenza (a TLR7 ligand) but responded normally to CpG ODN (TLR9 ligand) and Guardiquimod (TLR7 ligand). All three ligands activate plasmacytoid dendritic cells (pDCs). While there was a modest decline in pDC frequency in older individuals, there was no defect in uptake of influenza by geriatric pDCs.

Discussion and Conclusion

Influenza-induced production of IFN-alpha was defective in geriatric PBMCs by a mechanism that was independent of reduced pDC frequency or viability, defects in uptake of influenza, inability to secrete IFN-alpha, or defects in TLR7 signaling.

Keywords

Aging influenza interferon-alpha plasmacytoid dendritic cells

Abbreviations

ASA

Aspirin

CAD

Coronary artery disease

COPD

Chronic obstructive pulmonary disease

CVA

Cerebrovascular accident

DC

Dendritic cell

IFN

Interferon

PBMCs

Peripheral blood mononuclear cells

pDC

Plasmacytoid DC

TLR

Toll-like receptor

Copyright information

© Springer Science+Business Media, LLC 2010