title: Defects in the interferon-gamma and interleukin-12 pathways.
abstract: The interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway is a pivotal player in the immune system and is central to controlling mycobacterial infections. We highlight the most recent and relevant advances in understanding this pathway and their repercussions on basic and clinical science. Human mutations in IFN-gamma receptor-1 (IFN-gammaR1), IFN-gammaR2, IL-12p40, IL-12 receptor-beta1, signal transducer and activator of transcription-1, and nuclear factor-kappaB essential modulator are analyzed in the context of genetic susceptibility to mycobacterial diseases. A diagnostic and therapeutic approach is described. The IFN-gamma/IL-12 pathway is central in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the IFN-gamma/IL-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 genes in this pathway, some of which have therapeutic implications.
authors.affiliation: Division of Immunology, Department of Pediatrics, Hospital Nacional de Pediatría Juan P. Garrahan, Buenos Aires, Argentina.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Rosenzweig
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics*; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D009164:Mycobacterium Infections / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics*; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics*; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D004268:DNA-Binding Proteins; D051550:I-kappa B Kinase; D007371:Interferon-gamma; D018664:Interleukin-12; D017346:Protein Serine-Threonine Kinases; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C508438:IL12RB1 protein, human; C494079:STAT1 protein, human; C496559:CHUK protein, human; C496560:IKBKB protein, human; C496565:IKBKE protein, human