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preLekára.sk / Odborné časopisy / PLOS Pathogens / 2015 - 3

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

Souhrn

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.

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Článek Spatiotemporal Regulation of a T4SS Substrate by the Metaeffector SidJ
Článek Antigenic Properties of the Human Immunodeficiency Virus Envelope Glycoprotein Gp120 on Virions Bound to Target Cells
Článek Dependence of Intracellular and Exosomal microRNAs on Viral Oncogene Expression in HPV-positive Tumor Cells
Článek Identification of a Peptide-Pheromone that Enhances Escape from Host Cell Vacuoles
Článek Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Dihydrobiopterin in Adult Falciparum Malaria: Association with Disease Severity, Impaired Microvascular Function and Increased Endothelial Activation
Článek Transgenic Expression of the Dicotyledonous Pattern Recognition Receptor EFR in Rice Leads to Ligand-Dependent Activation of Defense Responses
Článek Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer
Článek Low Doses of Imatinib Induce Myelopoiesis and Enhance Host Anti-microbial Immunity
Článek Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Oxidized Biopterins in Pediatric Falciparum Malaria: Association with Disease Severity
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PLOS Pathogens

2015 Číslo 3
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Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
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