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

Autor: Duan X; Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen, 518112, P. R. China.; School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, P. R. China.; Shenzhen Center for Disease, Control and Prevention, Shenzhen, 518055, P.R. China., Boo ZZ; School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore., Chua SL; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, P. R. China., Chong KHC; School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore., Long Z; School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore., Yang R; School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore., Zhou Y; Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen, 518112, P. R. China.; School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, P. R. China., Janela B; Skin Research Institute of Singapore, Singapore, 308232, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 639798, Singapore., Chotirmall SH; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 639798, Singapore., Ginhoux F; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore, 138648, Singapore., Hu Q; Shenzhen Center for Disease, Control and Prevention, Shenzhen, 518055, P.R. China., Wu B; School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore.; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore., Yang L; Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Shenzhen, 518112, P. R. China.; School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, P. R. China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Dec; Vol. 10 (34), pp. e2304891. Date of Electronic Publication: 2023 Oct 23.
DOI: 10.1002/advs.202304891
Abstrakt: 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.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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