2. Academic Validation
  3. IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes

IRGB10 Liberates Bacterial Ligands for Sensing by the AIM2 and Caspase-11-NLRP3 Inflammasomes

  • Cell. 2016 Oct 6;167(2):382-396.e17. doi: 10.1016/j.cell.2016.09.012.
Si Ming Man 1,  Rajendra Karki 1,  Miwa Sasai 2,  David E Place 1,  Sannula Kesavardhana 1,  Jamshid Temirov 3,  Sharon Frase 4,  Qifan Zhu 5,  R K Subbarao Malireddi 1,  Teneema Kuriakose 1,  Jennifer L Peters 3,  Geoffrey Neale 6,  Scott A Brown 1,  Masahiro Yamamoto 2,  Thirumala-Devi Kanneganti 7
Affiliations

Affiliations

  • 1 Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • 2 Department of Immunoparasitology, Research Institute for Microbial Diseases, Laboratory of Immunoparasitology, World Premier International Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
  • 3 Department of Cellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • 4 Cell and Tissue Imaging Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • 5 Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
  • 6 Hartwell Center for Bioinformatics & Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • 7 Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: thirumala-devi.kanneganti@stjude.org.
PMID: 27693356 DOI: 10.1016/j.cell.2016.09.012
Abstract

The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of Caspase-1, Pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria. IRGB10 directly targeted cytoplasmic bacteria through a mechanism requiring guanylate-binding proteins. Localization of IRGB10 to the Bacterial cell membrane compromised Bacterial structural integrity and mediated cytosolic release of ligands for recognition by inflammasome sensors. Overall, our results reveal IRGB10 as part of a conserved signaling hub at the interface between cell-autonomous immunity and innate immune sensing pathways.

Keywords

GBP2; GBP5; GBPs; LPS; caspase-1; cell-autonomous immunity; immunity-related GTPases; innate immunity; interferons; non-canonical inflammasome.

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