Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists

The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective...

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Bibliographic Details
Published in:GeroScience 2022-10, Vol.44 (5), p.2555-2572
Main Authors: Connors, Jennifer, Taramangalam, Bhavani, Cusimano, Gina, Bell, Matthew R., Matt, Stephanie M., Runner, Kaitlyn, Gaskill, Peter J., DeFilippis, Victor, Nikolich-Žugich, Janko, Kutzler, Michele A., Haddad, Elias K.
Format: Article
Language:English
Subjects:
Aged
Aging
Agonists
Antigen presentation
Antiviral Agents
Antiviral drugs
Biomedical and Life Sciences
CD4 antigen
Cell Biology
Dendritic cells
Geriatrics/Gerontology
Humans
Immunity, Innate
Innate immunity
Interferon
Kinases
Life Sciences
Lymphocytes T
Molecular Medicine
Molecular modelling
Monocytes
Older people
Original
Original Article
Pattern recognition receptors
Phagocytosis
Public health
Receptors, Pattern Recognition
Signal Transduction
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Summary:The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described. Herein, we studied two critical pathways important in the production of type I interferon (IFN), the interferon response factor 7 (pIRF7), and TANK-binding kinase (pTBK-1). We show a decrease in pIRF7 and pTBK-1 in cross-priming dendritic cells (cDC1s), CD4 + T cell priming DCs (cDC2s), and CD14 dim CD16 + vascular patrolling monocytes from older adults ( n  = 11) following stimulation with pathway-specific agonists in comparison with young individuals ( n  = 11). The decrease in these key antiviral pathway proteins correlates with decreased phagocytosis, suggesting impaired function in Overall, our findings describe molecular mechanisms which explain the innate functional impairment in older adults and thus could inform us of novel approaches to restore these defects. Graphical abstract
ISSN:2509-2715
2509-2723
DOI:10.1007/s11357-022-00612-5