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Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria

Author

Listed:
  • José Carlos Santos

    (University of Lausanne)

  • Dave Boucher

    (University of Lausanne)

  • Larisa Kapinos Schneider

    (Biozentrum, University of Basel)

  • Benjamin Demarco

    (University of Lausanne)

  • Marisa Dilucca

    (University of Lausanne)

  • Kateryna Shkarina

    (University of Lausanne)

  • Rosalie Heilig

    (University of Lausanne)

  • Kaiwen W. Chen

    (University of Lausanne)

  • Roderick Y. H. Lim

    (Biozentrum, University of Basel)

  • Petr Broz

    (University of Lausanne)

Abstract

The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic Salmonella seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling.

Suggested Citation

  • José Carlos Santos & Dave Boucher & Larisa Kapinos Schneider & Benjamin Demarco & Marisa Dilucca & Kateryna Shkarina & Rosalie Heilig & Kaiwen W. Chen & Roderick Y. H. Lim & Petr Broz, 2020. "Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16889-z
    DOI: 10.1038/s41467-020-16889-z
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    Cited by:

    1. Shouya Feng & Daniel Enosi Tuipulotu & Abhimanu Pandey & Weidong Jing & Cheng Shen & Chinh Ngo & Melkamu B. Tessema & Fei-Ju Li & Daniel Fox & Anukriti Mathur & Anyang Zhao & Runli Wang & Klaus Pfeffe, 2022. "Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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