Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection
Bacterial infection tendentiously triggers inflammasome activation, whereas the roles of inflammasome activation in host defense against diverse infections remain unclear. Here, we identified that an ASC-dependent inflammasome activation played opposite roles in host defense against Francisella novi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.743335/full |
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| author | Yu Guo Yu Guo Rudi Mao Qingqing Xie Xiaojie Cheng Tao Xu Xiaoyuan Wang Yan Du Yan Du Xiaopeng Qi Xiaopeng Qi Xiaopeng Qi |
| author_facet | Yu Guo Yu Guo Rudi Mao Qingqing Xie Xiaojie Cheng Tao Xu Xiaoyuan Wang Yan Du Yan Du Xiaopeng Qi Xiaopeng Qi Xiaopeng Qi |
| author_sort | Yu Guo |
| collection | DOAJ |
| description | Bacterial infection tendentiously triggers inflammasome activation, whereas the roles of inflammasome activation in host defense against diverse infections remain unclear. Here, we identified that an ASC-dependent inflammasome activation played opposite roles in host defense against Francisella novicida wild-type (WT) U112 and mutant strain XWK4. Comparing with U112, XWK4 infection induced robust cytokine production, ASC-dependent inflammasome activation, and pyroptosis. Both AIM2 and NLRP3 were involved and played independent roles in XWK4-induced inflammasome activation. Type II interferon was partially required for XWK4-triggered inflammasome activation, which was different from type I interferon dependency in U112-induced inflammasome activation. Distinct from F. novicida U112 and Acinetobacter baumannii infection, Asc–/– mice were more resistant than WT mice response to XWK4 infection by limiting bacterial burden in vivo. The excessive inflammasome activation triggered by XWK4 infection caused dramatical cell death and pathological damage. Our study offers novel insights into mechanisms of inflammasome activation in host defense and provides potential therapeutic approach against bacterial infections and inflammatory diseases. |
| first_indexed | 2024-12-20T03:15:06Z |
| format | Article |
| id | doaj.art-25f9f56fa42e4f47a6087e827c382998 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-20T03:15:06Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-25f9f56fa42e4f47a6087e827c3829982022-12-21T19:55:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.743335743335Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring InfectionYu Guo0Yu Guo1Rudi Mao2Qingqing Xie3Xiaojie Cheng4Tao Xu5Xiaoyuan Wang6Yan Du7Yan Du8Xiaopeng Qi9Xiaopeng Qi10Xiaopeng Qi11School of Life Sciences, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaKey Laboratory for Experimental Teratology of the Ministry of Education, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory for Experimental Teratology of the Ministry of Education, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory for Experimental Teratology of the Ministry of Education, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaYunnan Key Laboratory of Laboratory Medicine, Kunming, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaKey Laboratory for Experimental Teratology of the Ministry of Education, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, ChinaBacterial infection tendentiously triggers inflammasome activation, whereas the roles of inflammasome activation in host defense against diverse infections remain unclear. Here, we identified that an ASC-dependent inflammasome activation played opposite roles in host defense against Francisella novicida wild-type (WT) U112 and mutant strain XWK4. Comparing with U112, XWK4 infection induced robust cytokine production, ASC-dependent inflammasome activation, and pyroptosis. Both AIM2 and NLRP3 were involved and played independent roles in XWK4-induced inflammasome activation. Type II interferon was partially required for XWK4-triggered inflammasome activation, which was different from type I interferon dependency in U112-induced inflammasome activation. Distinct from F. novicida U112 and Acinetobacter baumannii infection, Asc–/– mice were more resistant than WT mice response to XWK4 infection by limiting bacterial burden in vivo. The excessive inflammasome activation triggered by XWK4 infection caused dramatical cell death and pathological damage. Our study offers novel insights into mechanisms of inflammasome activation in host defense and provides potential therapeutic approach against bacterial infections and inflammatory diseases.https://www.frontiersin.org/articles/10.3389/fcell.2021.743335/fullFrancisella novicidaXWK4AIM2NLRP3ASC |
| spellingShingle | Yu Guo Yu Guo Rudi Mao Qingqing Xie Xiaojie Cheng Tao Xu Xiaoyuan Wang Yan Du Yan Du Xiaopeng Qi Xiaopeng Qi Xiaopeng Qi Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection Frontiers in Cell and Developmental Biology Francisella novicida XWK4 AIM2 NLRP3 ASC |
| title | Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection |
| title_full | Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection |
| title_fullStr | Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection |
| title_full_unstemmed | Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection |
| title_short | Francisella novicida Mutant XWK4 Triggers Robust Inflammasome Activation Favoring Infection |
| title_sort | francisella novicida mutant xwk4 triggers robust inflammasome activation favoring infection |
| topic | Francisella novicida XWK4 AIM2 NLRP3 ASC |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.743335/full |
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