Induction of Interferon-Stimulated Genes by IRF3 Promotes Replication of

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Interferon Regulatory Factor 3 (IRF3) is an essential transcription factor for the expression of antiviral genes, including type I IFNs and ISGs. The coordinated action of the ISGs leads to the inhibition of one or multiple steps of viral life cycle. In contrast to the well-known antiviral function of IRF3, we report here an unexpected pro-parasitic role of IRF3 in supporting the replication of the protozoan parasite, Toxoplasma gondii, in both cells and mice. The IRF3-deficient mice did not support T. gondii replication and, therefore, were protected from T. gondii-induced pathogenesis. The novel pro-Toxoplasma role of IRF3 was type I IFN-independent, but required its transcriptional function that induced the effector ISGs. Using cells deficient in known components of the IRF3 activation pathways, we have delineated the nature of the pro-parasitic signaling pathway, which we named ‘PISA’. Our detailed genetic and biochemical analyses revealed that PISA is activated by a T. gondii-triggered cytoplasmic cGAS/STING/TBK1-dependent pathway that activates IRF3 for the induction of the pro-parasitic ISGs.

Vyšlo v časopise: Induction of Interferon-Stimulated Genes by IRF3 Promotes Replication of. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004779
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004779

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