Mendelian susceptibility to mycobacterial disease

The host response to mycobacterial infection is mediated by the type I cytokine pathway (cell-mediated immunity). Deficiencies in this response result in susceptibility to poorly pathogenic mycobacterial species such as bacille Calmette-Guérin and environmental mycobacteria. In recent years a number of mutations in the genes encoding major components in the type I cytokine axis have been described which predispose to disseminated infection with these weakly virulent mycobacterial species. Affected individuals are also prone to extra-intestinal disease caused by non-typhoidal Salmonella. The genes involved display a high level of allelic heterogeneity, accounting for a number of distinct genetic disorders which vary in their mode of inheritance and clinical presentation. These disorders have been termed Mendelian susceptibility to mycobacterial disease and are discussed in this review article.