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Interferon-induced guanylate-binding proteins in inflammasome activation and host defense

Nature Immunology volume 17, pages 481–489 (2016)Cite this article

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Abstract

Traditional views of the inflammasome highlight the assembly of pre-existing core components shortly after infection or tissue damage. Emerging work, however, suggests that the inflammasome machinery is also subject to 'tunable' or inducible signals that might accelerate its autocatalytic properties and dictate where inflammasome assembly takes place in the cell. Many of these signals operate downstream of interferon receptors to elicit inflammasome regulators, including a new family of interferon-induced GTPases called 'guanylate-binding proteins' (GBPs). Here we investigate the critical roles of interferon-induced GBPs in directing inflammasome subtype–specific responses and their consequences for cell-autonomous immunity to a wide variety of microbial pathogens. We discuss emerging mechanisms of action and the potential effect of these GBPs on predisposition to sepsis and other infectious or inflammatory diseases.

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Figure 1: Evolutionary links between GBPs and the inflammasome machinery gleaned from fossil-record studies.
Figure 2: Familial and structural properties of the GBPs.
Figure 3: Specific steps at which individual GBPs affect canonical versus non-canonical inflammasome cascades.
Figure 4: Molecular mechanisms of GBPs in inflammasome activation.

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Acknowledgements

Supported by the HHMI Investigator Program, NIH NIAID (R01 AI068041-10 and R01 AI108834-02), the American Asthma Foundation Research Program (14-0073) and the Rainin Foundation (14H7).

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA

    Bae-Hoon Kim & John D MacMicking

  2. Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA

    Bae-Hoon Kim, Jonathan D Chee, Clinton J Bradfield, Eui-Soon Park, Pradeep Kumar & John D MacMicking

  3. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    John D MacMicking

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Kim, BH., Chee, J., Bradfield, C. et al. Interferon-induced guanylate-binding proteins in inflammasome activation and host defense. Nat Immunol 17, 481–489 (2016). https://doi.org/10.1038/ni.3440

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