Two tools used by the immune system to fight viruses and bacteria are the interferons IFNα/β and IFNγ. These cytokines induce the transcription of antiviral and antibacterial response genes via the recruitment of signal transducer and activator of transcription (STAT)-1 proteins. In a study of naturally occurring mutations, Dupuis et al. show that STAT-1 may direct immunity to viruses and bacteria through distinct pathways. A mutation that diminished phosphorylation of a specific tyrosine residue acted in a dominant-negative fashion to prevent the nuclear translocation of homotypic STAT-1 transcriptional complexes. In turn, this mutation correlated with a severe impairment of immune responses of individuals carrying the mutation to nonvirulent forms of mycobacteria. Remarkably, the same mutation did not affect viral immune responses and correlated with relatively normal nuclear translocation of a second heterotrimeric complex involving STAT-1.
S. Dupuis, C. Dargemont, C. Fieschi, N. Thomassin, S. Rosenzweig, J. Harris, S. M. Holland, R. D. Schreiber, J.-L. Casanova, Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. Science 293, 300-303 (2001). [Abstract] [Full Text]