These cases revealed the indispensable role of human intrinsic (TLR3, IRF7, IRF9, STAT1, and STAT2 in RECs, in which the virus replicates) and innate (IRF7 in plasmacytoid dendritic cells, in which the virus does not replicate) type I and III IFN immunity in host defense against influenza (Casanova and Abel, 2021b, 2022; Duncan et al., 2021; Manry et al., 2022; Zhang et al., 2022). The gene discussed is TLR3; the disease is influenza.