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Impairment of Mycobacterial but Not Viral Immunity by a Germline Human STAT1 Mutation
Ist Teil von
Science (American Association for the Advancement of Science), 2001-07, Vol.293 (5528), p.300-303
Ort / Verlag
Washington, DC: American Society for the Advancement of Science
Erscheinungsjahr
2001
Quelle
MEDLINE
Beschreibungen/Notizen
Interferons (IFN) α/β and γ induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.