A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors
Innate immune adaptor proteins are critical components of the innate immune system that propagate pro-inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/172985 |
| _version_ | 1826123338142973952 |
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| author | Duan, Xiangke Boo, Zhao Zhi Chua, Song Lin Chong, Kelvin Han Chung Long, Ziqi Yang, Renliang Zhou, Yachun Janela, Baptiste Chotirmall, Sanjay Haresh Ginhoux, Florent Hu, Qinghua Wu, Bin Yang, Liang |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Duan, Xiangke Boo, Zhao Zhi Chua, Song Lin Chong, Kelvin Han Chung Long, Ziqi Yang, Renliang Zhou, Yachun Janela, Baptiste Chotirmall, Sanjay Haresh Ginhoux, Florent Hu, Qinghua Wu, Bin Yang, Liang |
| author_sort | Duan, Xiangke |
| collection | NTU |
| description | Innate immune adaptor proteins are critical components of the innate immune system that propagate pro-inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the innate immune surveillance in ways that are still not fully understood. Here, it is reported that Pseudomonas aeruginosa induces its quorum sensing mechanism after macrophage engulfment. Further investigation of its secretome identified a quorum sensing regulated product, LasB, is responsible for innate immune suppression depending on the MyD88-mediated signaling. Moreover, it is showed that this specific type of pathogen-mediated innate immune suppression is due to the enzymatic digestion of the death domains of the innate immune adaptors, mainly MyD88, and attributed to LasB's large substrate binding groove. Lastly, it is demonstrated that the secretion of LasB from P. aeruginosa directly contributed to MyD88 degradation within macrophages. Hence, it is discovered an example of bacterial quorum sensing-regulated cellular innate immune suppression by direct cleavage of immune adaptors. |
| first_indexed | 2024-10-01T06:03:01Z |
| format | Journal Article |
| id | ntu-10356/172985 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:03:01Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1729852024-01-14T15:38:45Z A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors Duan, Xiangke Boo, Zhao Zhi Chua, Song Lin Chong, Kelvin Han Chung Long, Ziqi Yang, Renliang Zhou, Yachun Janela, Baptiste Chotirmall, Sanjay Haresh Ginhoux, Florent Hu, Qinghua Wu, Bin Yang, Liang Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Skin Research Institute of Singapore NTU Institute of Structural Biology Science::Medicine Host-Microbe Interaction Pseudomonas Aeruginosa Innate immune adaptor proteins are critical components of the innate immune system that propagate pro-inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the innate immune surveillance in ways that are still not fully understood. Here, it is reported that Pseudomonas aeruginosa induces its quorum sensing mechanism after macrophage engulfment. Further investigation of its secretome identified a quorum sensing regulated product, LasB, is responsible for innate immune suppression depending on the MyD88-mediated signaling. Moreover, it is showed that this specific type of pathogen-mediated innate immune suppression is due to the enzymatic digestion of the death domains of the innate immune adaptors, mainly MyD88, and attributed to LasB's large substrate binding groove. Lastly, it is demonstrated that the secretion of LasB from P. aeruginosa directly contributed to MyD88 degradation within macrophages. Hence, it is discovered an example of bacterial quorum sensing-regulated cellular innate immune suppression by direct cleavage of immune adaptors. Ministry of Education (MOE) Nanyang Technological University Published version This work was supported by the by, the National Key Research and Development Program of China (2022YFC2304700), the National Natural Science Foundation of China (32270196, 32200053), the Shenzhen Overseas High-level Talent Team (KQTD20200909113758004), the Guangdong Ba-sic And Applied Basic Research Foundation (2022B1515120075), the Ministry of Education of Singapore (MOE2016-T2-1-010, to L.Y. and B. W.), and Nanyang Technological University NAP-SUG to B.W. 2024-01-08T02:02:43Z 2024-01-08T02:02:43Z 2023 Journal Article Duan, X., Boo, Z. Z., Chua, S. L., Chong, K. H. C., Long, Z., Yang, R., Zhou, Y., Janela, B., Chotirmall, S. H., Ginhoux, F., Hu, Q., Wu, B. & Yang, L. (2023). A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors. Advanced Science, 10(34), e2304891-. https://dx.doi.org/10.1002/advs.202304891 2198-3844 https://hdl.handle.net/10356/172985 10.1002/advs.202304891 37870218 2-s2.0-85174572175 34 10 e2304891 en MOE2016-T2-1-010 Advanced Science © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. application/pdf |
| spellingShingle | Science::Medicine Host-Microbe Interaction Pseudomonas Aeruginosa Duan, Xiangke Boo, Zhao Zhi Chua, Song Lin Chong, Kelvin Han Chung Long, Ziqi Yang, Renliang Zhou, Yachun Janela, Baptiste Chotirmall, Sanjay Haresh Ginhoux, Florent Hu, Qinghua Wu, Bin Yang, Liang A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| title | A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| title_full | A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| title_fullStr | A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| title_full_unstemmed | A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| title_short | A bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| title_sort | bacterial quorum sensing regulated protease inhibits host immune responses by cleaving death domains of innate immune adaptors |
| topic | Science::Medicine Host-Microbe Interaction Pseudomonas Aeruginosa |
| url | https://hdl.handle.net/10356/172985 |
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