The data reported here, together with the recent description of disseminated environmental mycobacterial disease in an IL-23R-deficient patient (67), further suggest that human IL-23 is essential for host defense against even weakly virulent mycobacteria, as IL-23R deficiency underlies MSMD with complete penetrance in five unrelated kindreds with different and private IL23R genotypes. This evidence concerns the gene IL23R and Mendelian susceptibility to mycobacterial diseases.