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Translational control of the innate immune response through IRF-7

Author

Listed:
  • Rodney Colina

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Mauro Costa-Mattioli

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Ryan J. O. Dowling

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Maritza Jaramillo

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Lee-Hwa Tai

    (Institut de Recherches Cliniques de Montréal, Laboratory of Molecular Immunology, Université de Montréal, Montréal, Quebec H2W 1R7, Canada)

  • Caroline J. Breitbach

    (Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada)

  • Yvan Martineau

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Ola Larsson

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Liwei Rong

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Yuri V. Svitkin

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Andrew P. Makrigiannis

    (Institut de Recherches Cliniques de Montréal, Laboratory of Molecular Immunology, Université de Montréal, Montréal, Quebec H2W 1R7, Canada)

  • John C. Bell

    (Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada)

  • Nahum Sonenberg

    (McGill University, Montreal, Quebec H3G 1Y6, Canada)

Abstract

Transcriptional activation of cytokines, such as type-I interferons (interferon (IFN)-α and IFN-β), constitutes the first line of antiviral defence. Here we show that translational control is critical for induction of type-I IFN production. In mouse embryonic fibroblasts lacking the translational repressors 4E-BP1 and 4E-BP2, the threshold for eliciting type-I IFN production is lowered. Consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus and Sindbis virus is markedly suppressed. Furthermore, mice with both 4E- and 4E-BP2 genes (also known as Eif4ebp1 and Eif4ebp2, respectively) knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an enhanced type-I IFN production in plasmacytoid dendritic cells and the expression of IFN-regulated genes in the lungs. The enhanced type-I IFN response in 4E-BP1-/- 4E-BP2-/- double knockout mouse embryonic fibroblasts is caused by upregulation of interferon regulatory factor 7 (Irf7) messenger RNA translation. These findings highlight the role of 4E-BPs as negative regulators of type-I IFN production, via translational repression of Irf7 mRNA.

Suggested Citation

  • Rodney Colina & Mauro Costa-Mattioli & Ryan J. O. Dowling & Maritza Jaramillo & Lee-Hwa Tai & Caroline J. Breitbach & Yvan Martineau & Ola Larsson & Liwei Rong & Yuri V. Svitkin & Andrew P. Makrigiann, 2008. "Translational control of the innate immune response through IRF-7," Nature, Nature, vol. 452(7185), pages 323-328, March.
    • Handle: RePEc:nat:nature:v:452:y:2008:i:7185:d:10.1038_nature06730
    DOI: 10.1038/nature06730
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    Cited by:

    1. Huimei Chen & Gabriel Chew & Nithya Devapragash & Jui Zhi Loh & Kevin Y. Huang & Jing Guo & Shiyang Liu & Elisabeth Li Sa Tan & Shuang Chen & Nicole Gui Zhen Tee & Masum M. Mia & Manvendra K. Singh & , 2022. "The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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