Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa.
Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010305 |
| _version_ | 1811214579188891648 |
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| author | Karin Santoni David Pericat Leana Gorse Julien Buyck Miriam Pinilla Laure Prouvensier Salimata Bagayoko Audrey Hessel Stephen Adonai Leon-Icaza Elisabeth Bellard Serge Mazères Emilie Doz-Deblauwe Nathalie Winter Christophe Paget Jean-Philippe Girard Christine T N Pham Céline Cougoule Renaud Poincloux Mohamed Lamkanfi Emma Lefrançais Etienne Meunier Rémi Planès |
| author_facet | Karin Santoni David Pericat Leana Gorse Julien Buyck Miriam Pinilla Laure Prouvensier Salimata Bagayoko Audrey Hessel Stephen Adonai Leon-Icaza Elisabeth Bellard Serge Mazères Emilie Doz-Deblauwe Nathalie Winter Christophe Paget Jean-Philippe Girard Christine T N Pham Céline Cougoule Renaud Poincloux Mohamed Lamkanfi Emma Lefrançais Etienne Meunier Rémi Planès |
| author_sort | Karin Santoni |
| collection | DOAJ |
| description | Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa (P. aeruginosa) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P. aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P. aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1β secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P. aeruginosa-induced GSDMD activation triggers Calcium-dependent and Peptidyl Arginine Deaminase-4-driven histone citrullination and translocation of neutrophil DNA into the cell cytosol without inducing extracellular Neutrophil Extracellular Traps. Finally, we show that neutrophil Caspase-1 contributes to IL-1β production and susceptibility to pyroptosis-inducing P. aeruginosa strains in vivo. Overall, we demonstrate that neutrophils are not universally resistant for Caspase-1-dependent pyroptosis. |
| first_indexed | 2024-04-12T06:07:06Z |
| format | Article |
| id | doaj.art-3c1e9945786845ad89fa25728c4ad6f4 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-12T06:07:06Z |
| publishDate | 2022-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-3c1e9945786845ad89fa25728c4ad6f42022-12-22T03:44:50ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-07-01187e101030510.1371/journal.ppat.1010305Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa.Karin SantoniDavid PericatLeana GorseJulien BuyckMiriam PinillaLaure ProuvensierSalimata BagayokoAudrey HesselStephen Adonai Leon-IcazaElisabeth BellardSerge MazèresEmilie Doz-DeblauweNathalie WinterChristophe PagetJean-Philippe GirardChristine T N PhamCéline CougouleRenaud PoinclouxMohamed LamkanfiEmma LefrançaisEtienne MeunierRémi PlanèsMultiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa (P. aeruginosa) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P. aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P. aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1β secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P. aeruginosa-induced GSDMD activation triggers Calcium-dependent and Peptidyl Arginine Deaminase-4-driven histone citrullination and translocation of neutrophil DNA into the cell cytosol without inducing extracellular Neutrophil Extracellular Traps. Finally, we show that neutrophil Caspase-1 contributes to IL-1β production and susceptibility to pyroptosis-inducing P. aeruginosa strains in vivo. Overall, we demonstrate that neutrophils are not universally resistant for Caspase-1-dependent pyroptosis.https://doi.org/10.1371/journal.ppat.1010305 |
| spellingShingle | Karin Santoni David Pericat Leana Gorse Julien Buyck Miriam Pinilla Laure Prouvensier Salimata Bagayoko Audrey Hessel Stephen Adonai Leon-Icaza Elisabeth Bellard Serge Mazères Emilie Doz-Deblauwe Nathalie Winter Christophe Paget Jean-Philippe Girard Christine T N Pham Céline Cougoule Renaud Poincloux Mohamed Lamkanfi Emma Lefrançais Etienne Meunier Rémi Planès Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. PLoS Pathogens |
| title | Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. |
| title_full | Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. |
| title_fullStr | Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. |
| title_full_unstemmed | Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. |
| title_short | Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. |
| title_sort | caspase 1 driven neutrophil pyroptosis and its role in host susceptibility to pseudomonas aeruginosa |
| url | https://doi.org/10.1371/journal.ppat.1010305 |
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