Decreased phosphorylation of IRF7 and TBK-1 in CD14dimCD16+ monocytes, cDC1, and cDC2 from older donors impairs the production of IFN downstream of TLR7/8 and RIG-I pathways in primary antiviral responses and the ability of these cells to respond quickly to viral infection. Here, TBK1 is linked to viral infectious disease.