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The Signal Transducer and Activator of Transcription 1 (STAT1) is activated in response to interferons (IFNs) stimulations. In response to IFN- , STAT1 homodimerizes to form the gamma activating factor (GAF). In response to IFN- , STAT1 heterotrimerizes with STAT2 and ISGF3- to form the interferon sequence gene factor 3 (ISGF3). This work clearly demonstrates the distinct roles of the IFN- -induced-GAF complexes in anti-mycobacterial immunity and of IFN- induced- ISGF3 complexes in the anti-viral immunity in humans at the cellular and clinical levels by different molecular mechanisms. It also highlights the fact that a phenotype depends of the mutation and not only of the affected gene; and moreover the importance of the homozygosis or heterozygosis state of the mutation in human genetic diseases.
About the author
Ariane Chapgier presented this thesis to obtain the titles of Doctor in Genetics, and Doctor in Molecular Biology, speciality Immunology from Paris 7, and Vita-Salute San Raffaele Universities respectively. She obtained both titles with the highest mention, and her thesis has been evaluated to be in the top 10% of both universities in 2007.
