Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18.
Infection with Burkholderia pseudomallei or B. thailandensis triggers activation of the NLRP3 and NLRC4 inflammasomes leading to release of IL-1β and IL-18 and death of infected macrophages by pyroptosis, respectively. The non-canonical inflammasome composed of caspase-11 is also activated by these...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007105&type=printable |
| _version_ | 1826579482121601024 |
|---|---|
| author | Jinyong Wang Manoranjan Sahoo Louis Lantier Jonathan Warawa Hector Cordero Kelly Deobald Fabio Re |
| author_facet | Jinyong Wang Manoranjan Sahoo Louis Lantier Jonathan Warawa Hector Cordero Kelly Deobald Fabio Re |
| author_sort | Jinyong Wang |
| collection | DOAJ |
| description | Infection with Burkholderia pseudomallei or B. thailandensis triggers activation of the NLRP3 and NLRC4 inflammasomes leading to release of IL-1β and IL-18 and death of infected macrophages by pyroptosis, respectively. The non-canonical inflammasome composed of caspase-11 is also activated by these bacteria and provides protection through induction of pyroptosis. The recent generation of bona fide caspase-1-deficient mice allowed us to reexamine in a mouse model of pneumonic melioidosis the role of caspase-1 independently of caspase-11 (that was also absent in previously generated Casp1-/- mice). Mice lacking either caspase-1 or caspase-11 were significantly more susceptible than wild type mice to intranasal infection with B. thailandensis. Absence of caspase-1 completely abolished production of IL-1β and IL-18 as well as pyroptosis of infected macrophages. In contrast, in mice lacking caspase-11 IL-1β and IL-18 were produced at normal level and macrophages pyroptosis was only marginally affected. Adoptive transfer of bone marrow indicated that caspase-11 exerted its protective action both in myeloid cells and in radio-resistant cell types. B. thailandensis was shown to readily infect mouse lung epithelial cells triggering pyroptosis in a caspase-11-dependent way in vitro and in vivo. Importantly, we show that lung epithelial cells do not express inflammasomes components or caspase-1 suggesting that this cell type relies exclusively on caspase-11 for undergoing cell death in response to bacterial infection. Finally, we show that IL-18's protective action in melioidosis was completely dependent on its ability to induce IFNγ production. In turn, protection conferred by IFNγ against melioidosis was dependent on generation of ROS through the NADPH oxidase but independent of induction of caspase-11. Altogether, our results identify two non-redundant protective roles for caspase-1 and caspase-11 in melioidosis: Caspase-1 primarily controls pyroptosis of infected macrophages and production of IL-18. In contrast, caspase-11 mediates pyroptosis of infected lung epithelial cells. |
| first_indexed | 2024-12-21T01:20:22Z |
| format | Article |
| id | doaj.art-391aa9b13aaf4a279387f7ebb87c4294 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2025-03-14T14:18:58Z |
| publishDate | 2018-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-391aa9b13aaf4a279387f7ebb87c42942025-02-27T05:31:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-05-01145e100710510.1371/journal.ppat.1007105Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18.Jinyong WangManoranjan SahooLouis LantierJonathan WarawaHector CorderoKelly DeobaldFabio ReInfection with Burkholderia pseudomallei or B. thailandensis triggers activation of the NLRP3 and NLRC4 inflammasomes leading to release of IL-1β and IL-18 and death of infected macrophages by pyroptosis, respectively. The non-canonical inflammasome composed of caspase-11 is also activated by these bacteria and provides protection through induction of pyroptosis. The recent generation of bona fide caspase-1-deficient mice allowed us to reexamine in a mouse model of pneumonic melioidosis the role of caspase-1 independently of caspase-11 (that was also absent in previously generated Casp1-/- mice). Mice lacking either caspase-1 or caspase-11 were significantly more susceptible than wild type mice to intranasal infection with B. thailandensis. Absence of caspase-1 completely abolished production of IL-1β and IL-18 as well as pyroptosis of infected macrophages. In contrast, in mice lacking caspase-11 IL-1β and IL-18 were produced at normal level and macrophages pyroptosis was only marginally affected. Adoptive transfer of bone marrow indicated that caspase-11 exerted its protective action both in myeloid cells and in radio-resistant cell types. B. thailandensis was shown to readily infect mouse lung epithelial cells triggering pyroptosis in a caspase-11-dependent way in vitro and in vivo. Importantly, we show that lung epithelial cells do not express inflammasomes components or caspase-1 suggesting that this cell type relies exclusively on caspase-11 for undergoing cell death in response to bacterial infection. Finally, we show that IL-18's protective action in melioidosis was completely dependent on its ability to induce IFNγ production. In turn, protection conferred by IFNγ against melioidosis was dependent on generation of ROS through the NADPH oxidase but independent of induction of caspase-11. Altogether, our results identify two non-redundant protective roles for caspase-1 and caspase-11 in melioidosis: Caspase-1 primarily controls pyroptosis of infected macrophages and production of IL-18. In contrast, caspase-11 mediates pyroptosis of infected lung epithelial cells.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007105&type=printable |
| spellingShingle | Jinyong Wang Manoranjan Sahoo Louis Lantier Jonathan Warawa Hector Cordero Kelly Deobald Fabio Re Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. PLoS Pathogens |
| title | Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. |
| title_full | Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. |
| title_fullStr | Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. |
| title_full_unstemmed | Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. |
| title_short | Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL-18. |
| title_sort | caspase 11 dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase 1 mediates macrophage pyroptosis and production of il 18 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007105&type=printable |
| work_keys_str_mv | AT jinyongwang caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 AT manoranjansahoo caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 AT louislantier caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 AT jonathanwarawa caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 AT hectorcordero caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 AT kellydeobald caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 AT fabiore caspase11dependentpyroptosisoflungepithelialcellsprotectsfrommelioidosiswhilecaspase1mediatesmacrophagepyroptosisandproductionofil18 |