Innate Defects of the IL-12/IFN-γ Axis in Susceptibility to Infections by Mycobacteria and Salmonella

Since 1996, several studies characterizing the association between primary immunodeficiencies and susceptibility to infections with environmental and non-pathogenic mycobacteria such as the Bacillus Calmette-Guerin (Mycobacterium bovis Bacillus of Calmette Guerin strain) as well as disseminated infections by Salmonella spp. have been conducted. These conditions, grouped in the so-called Mendelian susceptibility to mycobacterial diseases, include a primary immunodeficiency caused by mutations in 7 autosomal genes (IFNGR1, IFNGR2, IL12B, IL12BR1, STAT1, ISG15, and IRF8) and an X-linked gene (NEMO). This syndrome presents a high degree of allelic heterogeneity and variable penetrance. This review focuses on the analysis of the first reported cases of these diseases, as well as on the molecular findings involved in each of them.