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Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome
Caspase-11 detection of intracellular lipopolysaccharide (LPS) from invasive Gram-negative bacteria mediates noncanonical activation of the NLRP3 inflammasome. While avirulent bacteria do not invade the cytosol, their presence in tissues necessitates clearance and immune system mobilization. Despite...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106893/ https://www.ncbi.nlm.nih.gov/pubmed/35487985 http://dx.doi.org/10.1038/s41590-022-01192-4 |
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author | Moretti, Julien Jia, Baosen Hutchins, Zachary Roy, Soumit Yip, Hilary Wu, Jiahui Shan, Meimei Jaffrey, Samie R. Coers, Jörn Blander, J. Magarian |
author_facet | Moretti, Julien Jia, Baosen Hutchins, Zachary Roy, Soumit Yip, Hilary Wu, Jiahui Shan, Meimei Jaffrey, Samie R. Coers, Jörn Blander, J. Magarian |
author_sort | Moretti, Julien |
collection | PubMed |
description | Caspase-11 detection of intracellular lipopolysaccharide (LPS) from invasive Gram-negative bacteria mediates noncanonical activation of the NLRP3 inflammasome. While avirulent bacteria do not invade the cytosol, their presence in tissues necessitates clearance and immune system mobilization. Despite sharing LPS, only live avirulent Gram-negative bacteria activate the NLRP3 inflammasome. Here, we found that bacterial mRNA, which signals bacterial viability, was required alongside LPS for noncanonical activation of the NLRP3 inflammasome in macrophages. Concurrent detection of bacterial RNA by NLRP3 and binding of LPS by procaspase-11 mediated a procaspase-11-NLRP3 interaction prior to caspase-11 activation and inflammasome assembly. LPS binding to procaspase-11 augmented bacterial mRNA-dependent assembly of the NLRP3 inflammasome, while bacterial viability and an assembled NLRP3 inflammasome were necessary for activation of LPS-bound procaspase-11. Thus, the procaspase-11-NLRP3 interaction nucleated a scaffold for their interdependent activation explaining their functional reciprocal exclusivity. Our findings inform novel vaccine adjuvant combinations and sepsis therapy. |
format | Online Article Text |
id | pubmed-9106893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-91068932022-10-29 Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome Moretti, Julien Jia, Baosen Hutchins, Zachary Roy, Soumit Yip, Hilary Wu, Jiahui Shan, Meimei Jaffrey, Samie R. Coers, Jörn Blander, J. Magarian Nat Immunol Article Caspase-11 detection of intracellular lipopolysaccharide (LPS) from invasive Gram-negative bacteria mediates noncanonical activation of the NLRP3 inflammasome. While avirulent bacteria do not invade the cytosol, their presence in tissues necessitates clearance and immune system mobilization. Despite sharing LPS, only live avirulent Gram-negative bacteria activate the NLRP3 inflammasome. Here, we found that bacterial mRNA, which signals bacterial viability, was required alongside LPS for noncanonical activation of the NLRP3 inflammasome in macrophages. Concurrent detection of bacterial RNA by NLRP3 and binding of LPS by procaspase-11 mediated a procaspase-11-NLRP3 interaction prior to caspase-11 activation and inflammasome assembly. LPS binding to procaspase-11 augmented bacterial mRNA-dependent assembly of the NLRP3 inflammasome, while bacterial viability and an assembled NLRP3 inflammasome were necessary for activation of LPS-bound procaspase-11. Thus, the procaspase-11-NLRP3 interaction nucleated a scaffold for their interdependent activation explaining their functional reciprocal exclusivity. Our findings inform novel vaccine adjuvant combinations and sepsis therapy. 2022-05 2022-04-29 /pmc/articles/PMC9106893/ /pubmed/35487985 http://dx.doi.org/10.1038/s41590-022-01192-4 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms |
spellingShingle | Article Moretti, Julien Jia, Baosen Hutchins, Zachary Roy, Soumit Yip, Hilary Wu, Jiahui Shan, Meimei Jaffrey, Samie R. Coers, Jörn Blander, J. Magarian Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome |
title | Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome |
title_full | Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome |
title_fullStr | Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome |
title_full_unstemmed | Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome |
title_short | Caspase-11 Interaction with NLRP3 Potentiates the Noncanonical Activation of the NLRP3 Inflammasome |
title_sort | caspase-11 interaction with nlrp3 potentiates the noncanonical activation of the nlrp3 inflammasome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106893/ https://www.ncbi.nlm.nih.gov/pubmed/35487985 http://dx.doi.org/10.1038/s41590-022-01192-4 |
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