The connection of IL-23 signaling to mycobacterial disease is based on the observation that IL23a−/− mice have impaired long-term control of pulmonary Mycobacterium tuberculosis infection [12], the fact that exogenous IL-23 can complement IL-12 deficiency for restoring mycobacterial immunity in mice [13], the association of a partial LOF variant c.1142G > A (R381Q) with active pulmonary tuberculosis [8] and the report of a kindred with MSMD harboring a homozygous complete LOF mutation in IL23R [7]. Here, IL23R is linked to Mendelian susceptibility to mycobacterial diseases.