Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death
Summary: Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720309931 |
| _version_ | 1818291941074272256 |
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| author | Daniel Fisch Barbara Clough Marie-Charlotte Domart Vesela Encheva Hironori Bando Ambrosius P. Snijders Lucy M. Collinson Masahiro Yamamoto Avinash R. Shenoy Eva-Maria Frickel |
| author_facet | Daniel Fisch Barbara Clough Marie-Charlotte Domart Vesela Encheva Hironori Bando Ambrosius P. Snijders Lucy M. Collinson Masahiro Yamamoto Avinash R. Shenoy Eva-Maria Frickel |
| author_sort | Daniel Fisch |
| collection | DOAJ |
| description | Summary: Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively. The pathogen-proximal detection-mechanisms of GBP1 remain poorly understood, as humans lack functional immunity-related GTPases (IRGs) that assist murine Gbps. Here, we establish that GBP1 promotes the lysis of Tg-containing vacuoles and parasite plasma membranes, releasing Tg-DNA. In contrast, we show GBP1 targets cytosolic STm and recruits caspase-4 to the bacterial surface for its activation by lipopolysaccharide (LPS), but does not contribute to bacterial vacuole escape. Caspase-1 cleaves and inactivates GBP1, and a cleavage-deficient GBP1D192E mutant increases caspase-4-driven pyroptosis due to the absence of feedback inhibition. Our studies elucidate microbe-specific roles of GBP1 in infection detection and its triggering of the assembly of divergent caspase signaling platforms. |
| first_indexed | 2024-12-13T02:52:03Z |
| format | Article |
| id | doaj.art-fcd45fd07738483588df111dbf4ade5d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T02:52:03Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fcd45fd07738483588df111dbf4ade5d2022-12-22T00:02:02ZengElsevierCell Reports2211-12472020-08-01326108008Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated DeathDaniel Fisch0Barbara Clough1Marie-Charlotte Domart2Vesela Encheva3Hironori Bando4Ambrosius P. Snijders5Lucy M. Collinson6Masahiro Yamamoto7Avinash R. Shenoy8Eva-Maria Frickel9Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London NW1 1AT, UK; MRC Centre for Molecular Bacteriology & Infection, Department of Infectious Disease, Imperial College London, London SW7 2AZ, UKHost-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London NW1 1AT, UKElectron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UKMass Spectrometry and Proteomics Platform, The Francis Crick Institute, London NW1 1AT, UKDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, JapanMass Spectrometry and Proteomics Platform, The Francis Crick Institute, London NW1 1AT, UKElectron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UKDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, JapanMRC Centre for Molecular Bacteriology & Infection, Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK; The Francis Crick Institute, London NW1 1AT, UK; Corresponding authorHost-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK; Corresponding authorSummary: Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively. The pathogen-proximal detection-mechanisms of GBP1 remain poorly understood, as humans lack functional immunity-related GTPases (IRGs) that assist murine Gbps. Here, we establish that GBP1 promotes the lysis of Tg-containing vacuoles and parasite plasma membranes, releasing Tg-DNA. In contrast, we show GBP1 targets cytosolic STm and recruits caspase-4 to the bacterial surface for its activation by lipopolysaccharide (LPS), but does not contribute to bacterial vacuole escape. Caspase-1 cleaves and inactivates GBP1, and a cleavage-deficient GBP1D192E mutant increases caspase-4-driven pyroptosis due to the absence of feedback inhibition. Our studies elucidate microbe-specific roles of GBP1 in infection detection and its triggering of the assembly of divergent caspase signaling platforms.http://www.sciencedirect.com/science/article/pii/S2211124720309931apoptosiscaspasesGBP1inflammasomespyroptosisSalmonella enterica Typhimurium |
| spellingShingle | Daniel Fisch Barbara Clough Marie-Charlotte Domart Vesela Encheva Hironori Bando Ambrosius P. Snijders Lucy M. Collinson Masahiro Yamamoto Avinash R. Shenoy Eva-Maria Frickel Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death Cell Reports apoptosis caspases GBP1 inflammasomes pyroptosis Salmonella enterica Typhimurium |
| title | Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death |
| title_full | Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death |
| title_fullStr | Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death |
| title_full_unstemmed | Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death |
| title_short | Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death |
| title_sort | human gbp1 differentially targets salmonella and toxoplasma to license recognition of microbial ligands and caspase mediated death |
| topic | apoptosis caspases GBP1 inflammasomes pyroptosis Salmonella enterica Typhimurium |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720309931 |
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