Geriatric adults have a significant defect in interferon-alpha production in response to influenza (133.50)

Abstract

Abstract Ninety percent of deaths attributed to influenza are in the elderly. While age-related decline in T cell function has been demonstrated, much less is known about the innate immune responses during natural infection and vaccination that shape humoral and cell mediated responses. We analyzed interferon alpha (IFN-alpha) production in peripheral blood mononuclear cells (PBMCs) isolated from younger adult and geriatric individuals that were stimulated with influenza or TLR ligands. A majority of geriatric PBMCs made significantly lower amounts of IFN-alpha, a signature anti-viral cytokine, in response to influenza. Surprisingly, geriatric PBMCs had normal production of IFN-alpha in response to the TLR9 ligand, CpG ODN, and the TLR7 ligand, guardiquimod. We determined that plasmacytoid dendritic cells (pDCs) are the main producers of IFN-alpha in response to influenza, CpG ODN and guardiquimod in PBMCs by cell depletion studies, and that influenza signals through TLR7. We are currently investigating the mechanism for this defect in IFN-alpha production in response to influenza by geriatric pDCs. A better understanding of the specific innate immune responses to influenza in geriatric individuals may allow a better understanding of the pathophysiology of the host-influenza interaction and therefore allow a more targeted approach to vaccine design. This work is supported by AI077056 and AI36219.