Interferon-γ and interleukin-12 pathway defects and human disease

A genetic component to human mycobacterial disease susceptibility has long been postulated. Over the past five years, mutations in the interferon-gamma (IFN gamma) receptor, IL-12 receptor beta 1 (IL-12R beta 1), and IL-12 p40 genes have been recognized. These mutations are associated with heightened susceptibility to disease caused by intracellular pathogens including nontuberculous mycobacteria, vaccine-associated bacille Calmette Guerin (BCG), Salmonella species, and some viruses. We describe the genotype-phenotype correlations in IFN gamma receptor, IL-12R beta 1, and IL-12 p40 deficiency, and discuss how study of these diseases has enhanced knowledge of human host defense against mycobacteria and other intracellular pathogens. Published by Elsevier Science Ltd.