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The Impact of Aging on Antiviral Pathways and Consequences for Immune Function
Journal article   Peer reviewed

The Impact of Aging on Antiviral Pathways and Consequences for Immune Function

Jennifer R Connors, Michele A. Kutzler and Elias Haddad
The Journal of immunology (1950), v 206(1_Supplement)
01 May 2021
DOI: https://doi.org/10.4049/jimmunol.206.Supp.13.04

Abstract

Abstract It is known that aging leads to increased morbidity and mortality, however, this has become more of a concern as the world population shifts to an increased percentage of older adults (>65) especially for COVID-19. These deaths may be from immunosenescence, a condition of chronic increased level of basal inflammation which can also result in diminished vaccine responses and immune system dysregulation, leading to COVID-19 complications. Current research shows a decrease in pro-inflammatory cytokines but the downstream signaling pathways in the context of aging have yet to be evaluated. Two critical pathway points in the production of type I IFN are the phosphorylation of pIRF7 in the TLR 7/8 pathway and of pTBK-1 in the RIG-I and cGAS-STING pathways. We show a decrease in pIRF7 and pTBK-1 in cDC1s, cDC2s, and CD14dimCD16+vascular patrolling monocytes from older adults (n=12) following stimulation with pathway specific agonists in comparison with healthy controls (n=12). This decrease correlates with decreased phagocytosis in the same cell subsets. These data support our previous reports of a delayed and decreased pro-inflammatory output following stimulation and demonstrate potential targets of antiviral pathways that can resolve dysfunctions of the aging immune system for an effective vaccination response. Therefore, we further hypothesize that cDC1, cDC2, and CD14dimCD16+ from older adults will have reduced antigen presentation and ability to cross-present viral peptides. We will utilize COVID-19 patient samples (n=110) to assess antigen-specificity of DCs and T cells in older COVID-19 pos. patients vs healthy controls (n=12).

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