Influenza-Induced Production of Interferon-Alpha is Defective in Geriatric Individuals
- 25 February 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Clinical Immunology
- Vol. 30 (3), 373-383
- https://doi.org/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
This publication has 73 references indexed in Scilit:
- Differential Recruitment of Dendritic Cells and Monocytes to Respiratory Mucosal Sites in Children with Influenza Virus or Respiratory Syncytial Virus InfectionThe Journal of Infectious Diseases, 2008
- Analysis of cytokine secretion from human plasmacytoid dendritic cells infected with H5N1 or low-pathogenicity influenza virusesVirology, 2008
- PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activationThe Journal of Experimental Medicine, 2008
- Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patientsThe Journal of Experimental Medicine, 2007
- Aging and T-cell diversityExperimental Gerontology, 2007
- The guinea pig as a transmission model for human influenza virusesProceedings of the National Academy of Sciences of the United States of America, 2006
- Spatiotemporal regulation of MyD88–IRF-7 signalling for robust type-I interferon inductionNature, 2005
- A structural perspective of the flavivirus life cycleNature Reviews Microbiology, 2005
- Cross-priming of CD8+ T cells stimulated by virus-induced type I interferonNature Immunology, 2003
- Antiviral actions of interferon interferon-regulated cellular proteins and their surprisingly selective antiviral activitiesVirology, 1991