A Bacterial Quorum Sensing Regulated Protease Inhibits Host Immune Responses by Cleaving Death Domains of Innate Immune Adaptors

Duan, Xiangke1,2,3; Boo, Zhao Zhi4,5; Chua, Song Lin6; Chong, Kelvin Han Chung4,5; Long, Ziqi4,5; Yang, Renliang4,5; Zhou, Yachun1,2; Janela, Baptiste7,9; Chotirmall, Sanjay Haresh9; Ginhoux, Florent8; Hu, Qinghua3; Wu, Bin4,5; Yang, Liang1,2

2023-10-01

10.1002/advs.202304891

ADVANCED SCIENCE   Impact Factor & Quartile

2198-3844

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.

host-microbe interaction innate immune adaptor MyD88 protease Pseudomonas aeruginosa quorum sensing

SCI

English

First ; Corresponding

The authors thank Dr. Ruedl Christiane for material and technical help. 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), t[2022YFC2304700] ; National Key Research and Development Program of China["32270196","32200053"] ; National Natural Science Foundation of China[KQTD20200909113758004] ; Shenzhen Overseas High-level Talent Team[2022B1515120075] ; Guangdong Basic And Applied Basic Research Foundation[MOE2016-T2-1-010]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001089489700001

WILEY

Web of Science

1.Southern Univ Sci & Technol, Affiliated Hosp 2, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Guangdong, Peoples R China
3.Shenzhen Ctr Dis Control & Prevent, Shenzhen 518055, Peoples R China
4.Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore
5.Nanyang Technol Univ, NTU Inst Struct Biol, Singapore 636921, Singapore
6.Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong 999077, Peoples R China
7.Skin Res Inst Singapore, Singapore 308232, Singapore
8.ASTAR, Singapore Immunol Network, 8A Biomed Grove, Singapore 138648, Singapore
9.Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore

Duan, Xiangke,Boo, Zhao Zhi,Chua, Song Lin,et al. A Bacterial Quorum Sensing Regulated Protease Inhibits Host Immune Responses by Cleaving Death Domains of Innate Immune Adaptors[J]. ADVANCED SCIENCE,2023.

Duan, Xiangke.,Boo, Zhao Zhi.,Chua, Song Lin.,Chong, Kelvin Han Chung.,Long, Ziqi.,...&Yang, Liang.(2023).A Bacterial Quorum Sensing Regulated Protease Inhibits Host Immune Responses by Cleaving Death Domains of Innate Immune Adaptors.ADVANCED SCIENCE.

Duan, Xiangke,et al."A Bacterial Quorum Sensing Regulated Protease Inhibits Host Immune Responses by Cleaving Death Domains of Innate Immune Adaptors".ADVANCED SCIENCE (2023).