Human deficiencies in type 1 cytokine receptors reveal the essential role of type 1 cytokines in immunity to intracellular bacteria.

Studies on patients with idiopathic, severe infections due to poorly pathogenic mycobacteria and Salmonella have revealed that many of these patients are unable to produce or respond to interferon-gamma (IFN-gamma). This inability results from causative, deleterious genetic mutations in either one of four different genes in the type 1 cytokine cascade, encoding interleukin-12Rbeta1 (IL-12Rbeta1), IL-12p40, IFN-gammaR1 or IFN-gammaR2. The immunological phenotypes resulting from the seven groups of complete or partial deficiencies in type 1 cytokine (receptor) genes that have been distinguished thus far will be summarized and discussed, and placed in a broader context in relation to disease susceptibility.