Cargando…
Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis
Despite intense research in understanding Clostridium perfringens (C. perfringens) pathogenesis, the mechanisms by which it is cleared from the host are largely unclarified. In C. perfringens gas gangrene and enterocolitis model, Mlkl(−/−) mice, lacking mixed lineage kinase-like protein (MLKL), are...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515590/ https://www.ncbi.nlm.nih.gov/pubmed/36185365 http://dx.doi.org/10.1016/j.isci.2022.105121 |
_version_ | 1784798518441934848 |
---|---|
author | Liu, Yang Xing, Li-Hua Li, Fen-Xin Wang, Na Ma, Yu-Ze Li, Jian-Wei Wu, Yu-Jing Liang, Jing Lei, Yu-Xin Wang, Xue-Yin Meng, Fan-Hua Yang, Yong-Jun Li, Guang-Peng Wang, Xiao Yu, Shui-Xing |
author_facet | Liu, Yang Xing, Li-Hua Li, Fen-Xin Wang, Na Ma, Yu-Ze Li, Jian-Wei Wu, Yu-Jing Liang, Jing Lei, Yu-Xin Wang, Xue-Yin Meng, Fan-Hua Yang, Yong-Jun Li, Guang-Peng Wang, Xiao Yu, Shui-Xing |
author_sort | Liu, Yang |
collection | PubMed |
description | Despite intense research in understanding Clostridium perfringens (C. perfringens) pathogenesis, the mechanisms by which it is cleared from the host are largely unclarified. In C. perfringens gas gangrene and enterocolitis model, Mlkl(−/−) mice, lacking mixed lineage kinase-like protein (MLKL), are more susceptible to C. perfringens infection. Mlkl deficiency results in a defect in inflammasome activation, and IL-18 and IL-1β releases. Exogenous administration of recombinant IL-18 is able to rescue the susceptibility of Mlkl(−/−) mice. Notably, K(+) efflux-dependent NLRP3 inflammasome signaling downstream of active MLKL promotes bacterial killing and clearance. Interestingly, the defect of bactericidal activity is also mediated by decreased classical extracellular trap formation in the absence of Mlkl. Our results demonstrate that MLKL mediates extracellular trap formation in a NLRP3 inflammasome-dependent manner. These findings highlight the requirement of MLKL for host defense against C. perfringens infection through enhancing NLRP3 inflammasome-extracellular traps axis. |
format | Online Article Text |
id | pubmed-9515590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-95155902022-09-29 Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis Liu, Yang Xing, Li-Hua Li, Fen-Xin Wang, Na Ma, Yu-Ze Li, Jian-Wei Wu, Yu-Jing Liang, Jing Lei, Yu-Xin Wang, Xue-Yin Meng, Fan-Hua Yang, Yong-Jun Li, Guang-Peng Wang, Xiao Yu, Shui-Xing iScience Article Despite intense research in understanding Clostridium perfringens (C. perfringens) pathogenesis, the mechanisms by which it is cleared from the host are largely unclarified. In C. perfringens gas gangrene and enterocolitis model, Mlkl(−/−) mice, lacking mixed lineage kinase-like protein (MLKL), are more susceptible to C. perfringens infection. Mlkl deficiency results in a defect in inflammasome activation, and IL-18 and IL-1β releases. Exogenous administration of recombinant IL-18 is able to rescue the susceptibility of Mlkl(−/−) mice. Notably, K(+) efflux-dependent NLRP3 inflammasome signaling downstream of active MLKL promotes bacterial killing and clearance. Interestingly, the defect of bactericidal activity is also mediated by decreased classical extracellular trap formation in the absence of Mlkl. Our results demonstrate that MLKL mediates extracellular trap formation in a NLRP3 inflammasome-dependent manner. These findings highlight the requirement of MLKL for host defense against C. perfringens infection through enhancing NLRP3 inflammasome-extracellular traps axis. Elsevier 2022-09-12 /pmc/articles/PMC9515590/ /pubmed/36185365 http://dx.doi.org/10.1016/j.isci.2022.105121 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Liu, Yang Xing, Li-Hua Li, Fen-Xin Wang, Na Ma, Yu-Ze Li, Jian-Wei Wu, Yu-Jing Liang, Jing Lei, Yu-Xin Wang, Xue-Yin Meng, Fan-Hua Yang, Yong-Jun Li, Guang-Peng Wang, Xiao Yu, Shui-Xing Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis |
title | Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis |
title_full | Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis |
title_fullStr | Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis |
title_full_unstemmed | Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis |
title_short | Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis |
title_sort | mixed lineage kinase-like protein protects against clostridium perfringens infection by enhancing nlrp3 inflammasome-extracellular traps axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515590/ https://www.ncbi.nlm.nih.gov/pubmed/36185365 http://dx.doi.org/10.1016/j.isci.2022.105121 |
work_keys_str_mv | AT liuyang mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT xinglihua mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT lifenxin mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT wangna mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT mayuze mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT lijianwei mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT wuyujing mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT liangjing mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT leiyuxin mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT wangxueyin mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT mengfanhua mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT yangyongjun mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT liguangpeng mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT wangxiao mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis AT yushuixing mixedlineagekinaselikeproteinprotectsagainstclostridiumperfringensinfectionbyenhancingnlrp3inflammasomeextracellulartrapsaxis |