Congenital defects in the interferon-gamma/interleukin-12 pathway.

PURPOSE OF REVIEW: The aim of this review is to highlight the most recent and relevant advances in the interferon-gamma/interleukin-12 pathway, a pivotal player of the immune system, and their repercussions on basic and clinical aspects of science.

RECENT FINDINGS: Newly described mutations are helping us to dissect the interferon-gamma/interleukin-12 pathway and its role in genetic infectious susceptibility and autoimmunity, and to reevaluate the pathophysiologic mechanisms involved in dominant and recessively inherited mutations.

SUMMARY: The interferon-gamma/interleukin-12 pathway plays a central role in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the interferon-gamma/interleukin-12 pathway is also involved in the pathogenesis of autoimmune disease, as well as tumor development and control. Genotype-phenotype correlations have been established for certain mutants in this pathway, some of which have therapeutic implications.