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Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation

Author

Listed:
  • Tali Lang

    (Monash University
    Cabrini Institute Malvern)

  • Jacinta P. W. Lee

    (Monash University)

  • Kirstin Elgass

    (Hudson Institute of Medical Research)

  • Anita A. Pinar

    (Monash University
    Monash University)

  • Michelle D. Tate

    (Hudson Institute of Medical Research
    Monash University)

  • Elizabeth H. Aitken

    (University of Melbourne)

  • Huapeng Fan

    (Monash University)

  • Sarah J. Creed

    (Hudson Institute of Medical Research)

  • Nadia S. Deen

    (Monash University)

  • Daouda A. K. Traore

    (Monash University
    Universite des Sciences Techniques et Technologiques de Bamako (USTTB))

  • Ivo Mueller

    (Walter and Eliza Hall Institute, Parkville
    University of Melbourne, Parkville
    Institut Pasteur)

  • Danielle Stanisic

    (Institute of Medical Research
    Griffith University)

  • Francesca S. Baiwog

    (Papua New Guinea Institute of Medical Research)

  • Colin Skene

    (University of Melbourne)

  • Matthew C. J. Wilce

    (Monash University)

  • Ashley Mansell

    (Hudson Institute of Medical Research
    Monash University)

  • Eric F. Morand

    (Monash University)

  • James Harris

    (Monash University)

Abstract

Macrophage migration inhibitory factor (MIF) exerts multiple effects on immune cells, as well as having functions outside the immune system. MIF can promote inflammation through the induction of other cytokines, including TNF, IL-6, and IL-1 family cytokines. Here, we show that inhibition of MIF regulates the release of IL-1α, IL-1β, and IL-18, not by affecting transcription or translation of these cytokines, but via activation of the NLRP3 inflammasome. MIF is required for the interaction between NLRP3 and the intermediate filament protein vimentin, which is critical for NLRP3 activation. Further, we demonstrate that MIF interacts with NLRP3, indicating a role for MIF in inflammasome activation independent of its role as a cytokine. These data advance our understanding of how MIF regulates inflammation and identify it as a factor critical for NLRP3 inflammasome activation.

Suggested Citation

  • Tali Lang & Jacinta P. W. Lee & Kirstin Elgass & Anita A. Pinar & Michelle D. Tate & Elizabeth H. Aitken & Huapeng Fan & Sarah J. Creed & Nadia S. Deen & Daouda A. K. Traore & Ivo Mueller & Danielle S, 2018. "Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04581-2
    DOI: 10.1038/s41467-018-04581-2
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