The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation
Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation an...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2258057 |
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| author | Yu-Xin Lei Yang Liu Li-Hua Xing Yu-Jing Wu Xue-Yin Wang Fan-Hua Meng Ya-Nan Lou Zhao-Guo Ma Lin Yuan Shui-Xing Yu |
| author_facet | Yu-Xin Lei Yang Liu Li-Hua Xing Yu-Jing Wu Xue-Yin Wang Fan-Hua Meng Ya-Nan Lou Zhao-Guo Ma Lin Yuan Shui-Xing Yu |
| author_sort | Yu-Xin Lei |
| collection | DOAJ |
| description | Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium, and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection. |
| format | Article |
| id | doaj-art-22680d7d94ae4436bf03c4e18d1e89a0 |
| institution | OA Journals |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-22680d7d94ae4436bf03c4e18d1e89a02025-08-20T02:38:22ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2258057The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formationYu-Xin Lei0Yang Liu1Li-Hua Xing2Yu-Jing Wu3Xue-Yin Wang4Fan-Hua Meng5Ya-Nan Lou6Zhao-Guo Ma7Lin Yuan8Shui-Xing Yu9State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaHost innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium, and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection.https://www.tandfonline.com/doi/10.1080/21505594.2023.2258057S. pluranimaliuminnate immunitymixed lineage kinase-like proteinNLRP3 inflammasomeextracellular trap |
| spellingShingle | Yu-Xin Lei Yang Liu Li-Hua Xing Yu-Jing Wu Xue-Yin Wang Fan-Hua Meng Ya-Nan Lou Zhao-Guo Ma Lin Yuan Shui-Xing Yu The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation Virulence S. pluranimalium innate immunity mixed lineage kinase-like protein NLRP3 inflammasome extracellular trap |
| title | The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation |
| title_full | The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation |
| title_fullStr | The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation |
| title_full_unstemmed | The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation |
| title_short | The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation |
| title_sort | pseudokinase mlkl contributes to host defense against streptococcus pluranimalium infection by mediating nlrp3 inflammasome activation and extracellular trap formation |
| topic | S. pluranimalium innate immunity mixed lineage kinase-like protein NLRP3 inflammasome extracellular trap |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2258057 |
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