Influenza-induced production of interferon-alpha is defective in geriatric individuals.
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.


CONCLUSIONS
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.
Canaday
David H
DH
Geriatric Research, Education and Clinical Center (GRECC), Cleveland VA Medical Center, Cleveland, OH 44106, USA.
Amponsah
Naa Ayele
NA
Jones
Leola
L
Tisch
Daniel J
DJ
Hornick
Thomas R
TR
Ramachandra
Lakshmi
L
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009975:Orthomyxoviridae / Q000276:immunology* / Q000472:pathogenicity; D051193:Toll-Like Receptors / Q000276:immunology
D016898:Interferon-alpha; D008024:Ligands; D051193:Toll-Like Receptors