Influenza-Induced Production of Interferon-Alpha is Defective in Geriatric Individuals
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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.
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.
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.
KeywordsAging influenza interferon-alpha plasmacytoid dendritic cells
Coronary artery disease
Chronic obstructive pulmonary disease
Peripheral blood mononuclear cells
This work was supported by AI077056 (to L.R. and D.C), McGregor Fund grant (to D.C) and Veterans Affairs GRECC and CSR&D Merit grant (D.C. and T.H.). Flow cytometry was performed at the CWRU/UH Center for AIDS Research (NIH Grant AI36219). We thank Megan Ermler for assistance with infecting Vero E6 cells, Scott Howell at Visual Sciences Research Center (NIH Grant P30-EY11373) for assistance with microscopy, Gareth Hardy for IFN-beta analysis and Lucy Jury at the Cleveland VA for help procuring blood samples.
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