The Combination of IFN β and TNF Induces an Antiviral and Immunoregulatory Program via Non-Canonical Pathways Involving STAT2 and IRF9

Autor: Mario Kalamujic, Mélissa K. Mariani, Sandra Cervantes-Ortiz, Pouria Dasmeh, Alexander N. Harrison, Espérance Mukawera, Elise Caron, Audray Fortin, Dacquin M. Kasumba, Adrian W.R. Serohijos, Diana Ioana Hotea, Nathalie Grandvaux
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Cells
Volume 8
Issue 8
Cells, Vol 8, Iss 8, p 919 (2019)
ISSN: 2073-4409
DOI: 10.3390/cells8080919
Popis: Interferon (IFN) &beta
and Tumor Necrosis Factor (TNF) are key players in immunity against viruses. Compelling evidence has shown that the antiviral and inflammatory transcriptional response induced by IFN&beta
is reprogrammed by crosstalk with TNF. IFN&beta
mainly induces interferon-stimulated genes by the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway involving the canonical ISGF3 transcriptional complex, composed of STAT1, STAT2, and IRF9. The signaling pathways engaged downstream of the combination of IFN&beta
and TNF remain elusive, but previous observations suggested the existence of a response independent of STAT1. Here, using genome-wide transcriptional analysis by RNASeq, we observed a broad antiviral and immunoregulatory response initiated in the absence of STAT1 upon IFN&beta
and TNF costimulation. Additional stratification of this transcriptional response revealed that STAT2 and IRF9 mediate the expression of a wide spectrum of genes. While a subset of genes was regulated by the concerted action of STAT2 and IRF9, other gene sets were independently regulated by STAT2 or IRF9. Collectively, our data supports a model in which STAT2 and IRF9 act through non-canonical parallel pathways to regulate distinct pool of antiviral and immunoregulatory genes in conditions with elevated levels of both IFN&beta
and TNF.
Databáze: OpenAIRE
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