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ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity
The inflammasome is a major regulator of inflammation through its activation of procaspase-1, which cleaves prointerleukin-1β (pro-IL-1β) into its mature form. IL-1β is a critical proinflammatory cytokine that dictates the severity of inflammation associated with a wide spectrum of inflammatory dise...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278538/ https://www.ncbi.nlm.nih.gov/pubmed/25538194 http://dx.doi.org/10.1128/mBio.02186-14 |
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author | Bose, Santanu Segovia, Jesus A. Somarajan, Sudha R. Chang, Te-Hung Kannan, T. R. Baseman, Joel B. |
author_facet | Bose, Santanu Segovia, Jesus A. Somarajan, Sudha R. Chang, Te-Hung Kannan, T. R. Baseman, Joel B. |
author_sort | Bose, Santanu |
collection | PubMed |
description | The inflammasome is a major regulator of inflammation through its activation of procaspase-1, which cleaves prointerleukin-1β (pro-IL-1β) into its mature form. IL-1β is a critical proinflammatory cytokine that dictates the severity of inflammation associated with a wide spectrum of inflammatory diseases. NLRP3 is a key component of the inflammasome complex, and multiple signals and stimuli trigger formation of the NLRP3 inflammasome complex. In the current study, we uncovered a yet unknown mechanism of NLRP3 inflammasome activation by a pathogen-derived factor. We show that the unique bacterial ADP-ribosylating and vacuolating toxin produced by Mycoplasma pneumoniae and designated community-acquired respiratory distress syndrome (CARDS) toxin activates the NLRP3 inflammasome by colocalizing with the NLRP3 inflammasome and catalyzing the ADP-ribosylation of NLRP3. Mutant full-length CARDS toxin lacking ADP-ribosyltransferase (ADPRT) activity and truncated CARDS toxins unable to bind to macrophages and be internalized failed to activate the NLRP3 inflammasome. These studies demonstrate that CARDS toxin-mediated ADP-ribosylation constitutes an important posttranslational modification of NLRP3, that ADPRT activity of CARDS toxin is essential for NLRP3 inflammasome activation, and that posttranslational ADPRT-mediated modification of the inflammasome is a newly discovered mechanism for inflammasome activation with subsequent release of IL-1β and associated pathologies. |
format | Online Article Text |
id | pubmed-4278538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-42785382014-12-31 ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity Bose, Santanu Segovia, Jesus A. Somarajan, Sudha R. Chang, Te-Hung Kannan, T. R. Baseman, Joel B. mBio Research Article The inflammasome is a major regulator of inflammation through its activation of procaspase-1, which cleaves prointerleukin-1β (pro-IL-1β) into its mature form. IL-1β is a critical proinflammatory cytokine that dictates the severity of inflammation associated with a wide spectrum of inflammatory diseases. NLRP3 is a key component of the inflammasome complex, and multiple signals and stimuli trigger formation of the NLRP3 inflammasome complex. In the current study, we uncovered a yet unknown mechanism of NLRP3 inflammasome activation by a pathogen-derived factor. We show that the unique bacterial ADP-ribosylating and vacuolating toxin produced by Mycoplasma pneumoniae and designated community-acquired respiratory distress syndrome (CARDS) toxin activates the NLRP3 inflammasome by colocalizing with the NLRP3 inflammasome and catalyzing the ADP-ribosylation of NLRP3. Mutant full-length CARDS toxin lacking ADP-ribosyltransferase (ADPRT) activity and truncated CARDS toxins unable to bind to macrophages and be internalized failed to activate the NLRP3 inflammasome. These studies demonstrate that CARDS toxin-mediated ADP-ribosylation constitutes an important posttranslational modification of NLRP3, that ADPRT activity of CARDS toxin is essential for NLRP3 inflammasome activation, and that posttranslational ADPRT-mediated modification of the inflammasome is a newly discovered mechanism for inflammasome activation with subsequent release of IL-1β and associated pathologies. American Society of Microbiology 2014-12-23 /pmc/articles/PMC4278538/ /pubmed/25538194 http://dx.doi.org/10.1128/mBio.02186-14 Text en Copyright © 2014 Bose et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bose, Santanu Segovia, Jesus A. Somarajan, Sudha R. Chang, Te-Hung Kannan, T. R. Baseman, Joel B. ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity |
title | ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity |
title_full | ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity |
title_fullStr | ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity |
title_full_unstemmed | ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity |
title_short | ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity |
title_sort | adp-ribosylation of nlrp3 by mycoplasma pneumoniae cards toxin regulates inflammasome activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278538/ https://www.ncbi.nlm.nih.gov/pubmed/25538194 http://dx.doi.org/10.1128/mBio.02186-14 |
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