Inborn errors of immunity resulting from single-gene defects have been shown to underlie multiple bacterial infections [myeloid differentiation primary response 88 (MYD88) and interleukin 1 receptor-associated kinase 4 (IRAK4) deficiency], monogenic susceptibility to mycobacterial disease (deficiency of genes in the IL12/IFN-γ loop), herpes simplex encephalitis (defect in TLR3-dependent immune responses), and severe primary Influenza virus infection (interferon regulatory factor 7 deficiency) (56–60). Here, IRAK4 is linked to herpes simplex encephalitis.