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Retour sur le Congrès International Keystone Symposium “Type I Interferon: Friend and Foe Alike” 2017

Retour sur le Congrès International Keystone Symposium “Type I Interferon: Friend and Foe Alike” 2017, Banff, Canada par Laura Sinigaglia, laureate d'une bourse de voyage CFCD.

The “Type I Interferon: Friend and Foe Alike” Keystone Symposium joint with the meeting “Pattern Recognition Signaling: From Innate Immunity to Inflammatory Disease” was organized by Alan Sher, Virginia Pascual, Adolfo García-Sastre and Anne O'Garra.

The meeting was centered on the functional dichotomy of Type I interferon(s) exemplified by the diverse activities in health and disease. Type I IFNs, discovered for their anti-viral activity, can also be detrimental and promote autoimmune diseases or favor bacterial and viral infection.

The quality of the conference was incredible, invited and selected speakers gave outstanding and inspiring talks. Here is the summary of some selected talks that I found particularly interesting.

Ana Fernandez-Sesma (Mount Sinai school of Medicine, USA) presented some recently published data. She aims at understanding the mechanisms by which Dengue virus (DV) can initiate and modulate the innate immune pathways in order to establish infection in the host. She showed that mitochondrial DNA is released in the cytoplasm during DV infection, triggering the cGAS/STING pathway. However, the viral protease is able to cleave STING, as well as promoting the degradation of cGAS. This results in the inhibition of type I IFN response in infected cells. This work is the first demonstration of a RNA virus counteracting IFN induction via a cellular DNA sensing pathway.

Sun Hur (Harvard Medical School, USA) gave a talk on the mechanism of discrimination between self and non-self RNAs by MDA5. She showed that long dsRNAs are better recognized by MDA5 than ssRNAs because MDA5 is forming long filaments along the dsRNA molecule which stability depends on the length of the dsRNA. Interestingly, heterozygous mutations in MDA5 are responsible for the Aicardi-Goutières syndrome (AGS). These mutations overstabilize MDA5 filaments; increasing sensitivity to uncharacterized cellular RNA, which in turn lead to excessive IFN production.

Finally, I particularly appreciated the talk of Joaquín M. Espinosa (University of Colorado Boulder, USA). He is promoting the message that Down syndrome is an Interferonopathy. He demonstrated by several approaches (i.e. transcriptome analyses, and shRNA kinome screens) that the interferon pathway is consistently activated by trisomy 21 and that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts. By employing a cohort of >250 individuals, and performing a plasma proteomics study, he showed massive immune dysregulation in people with Down syndrome, including changes in
many immune-modulatory factors that could be explained by chronic IFN hyperactivation. His observations could explain the hyperimmune phenotype of Down syndrome (high prevalence of diverse autoimmune disorders, protection against solid tumors, and neuroinflammation). Interestingly, he proposed that the interferon activation is due to the increased gene dosage of the four IFN receptors encoded on chromosome 21. For this he believes that interferon antagonists could have therapeutic benefits in Down syndrome.

I would like to thanks the CFCD for giving me the opportunity to attend this renowned international meeting, to present the results of my PhD project and to discuss exciting findings with world experts.