Journal Article

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

Connors, Jennifer, Matt, Stephanie M., Gaskill, Peter J., Kutzler, Michele A., Haddad, Elias K., Runner, Kaitlyn, Cusimano, Gina, DeFilippis, Victor, Bell, Matthew R., Taramangalam, Bhavani, Nikolich-Žugich, Janko

2022

Overview

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

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adults / Aged / Aging / Agonists / Antigen presentation / Antiviral Agents / Antiviral drugs / Biomedical and Life Sciences / CD4 antigen / Cell Biology / Critical pathways / Delayed / Dendritic cells / Function / Functional impairment / Geriatrics/Gerontology / Health problems / Humans / Immune response / Immunity / Immunity, Innate / Induction / Innate immunity / Interferon / Kinases / Life Sciences / Lymphocytes T / Molecular Medicine / Molecular modelling / Monocytes / Older people / Original / Original Article / Pattern recognition / Pattern recognition receptors / Phagocytosis / Population aging / Priming / Proteins / Public health / Receptors, Pattern Recognition / Signal Transduction / Stimulation / Vaccines / Volunteers / World population