S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens
Abstract Oxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46212-z |
| _version_ | 1827326808314347520 |
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| author | Mutian Jia Li Chai Jie Wang Mengge Wang Danhui Qin Hui Song Yue Fu Chunyuan Zhao Chengjiang Gao Jihui Jia Wei Zhao |
| author_facet | Mutian Jia Li Chai Jie Wang Mengge Wang Danhui Qin Hui Song Yue Fu Chunyuan Zhao Chengjiang Gao Jihui Jia Wei Zhao |
| author_sort | Mutian Jia |
| collection | DOAJ |
| description | Abstract Oxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by which the host enables innate immunity activation during oxidative burst remains largely unknown. Here, we demonstrate that S-nitrosoglutathione (GSNO), the main endogenous SNO, attenuates innate immune responses against herpes simplex virus-1 (HSV-1) and Listeria monocytogenes infections. Mechanistically, GSNO induces the S-nitrosylation of stimulator of interferon genes (STING) at Cys257, inhibiting its binding to the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Alcohol dehydrogenase 5 (ADH5), the key enzyme that metabolizes GSNO to decrease cellular SNOs, facilitates STING activation by inhibiting S-nitrosylation. Concordantly, Adh5 deficiency show defective STING-dependent immune responses upon microbial challenge and facilitates viral replication. Thus, cellular oxidative burst-induced RNS attenuates the STING-mediated innate immune responses to microbial infection, while ADH5 licenses STING activation by maintaining cellular SNO homeostasis. |
| first_indexed | 2024-03-07T14:51:55Z |
| format | Article |
| id | doaj.art-c45f289119884bd0994eb2449a9c3ed9 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:55Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c45f289119884bd0994eb2449a9c3ed92024-03-05T19:41:48ZengNature PortfolioNature Communications2041-17232024-02-0115111210.1038/s41467-024-46212-zS-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogensMutian Jia0Li Chai1Jie Wang2Mengge Wang3Danhui Qin4Hui Song5Yue Fu6Chunyuan Zhao7Chengjiang Gao8Jihui Jia9Wei Zhao10Department of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Cell Biology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Pathogenic Biology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract Oxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by which the host enables innate immunity activation during oxidative burst remains largely unknown. Here, we demonstrate that S-nitrosoglutathione (GSNO), the main endogenous SNO, attenuates innate immune responses against herpes simplex virus-1 (HSV-1) and Listeria monocytogenes infections. Mechanistically, GSNO induces the S-nitrosylation of stimulator of interferon genes (STING) at Cys257, inhibiting its binding to the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Alcohol dehydrogenase 5 (ADH5), the key enzyme that metabolizes GSNO to decrease cellular SNOs, facilitates STING activation by inhibiting S-nitrosylation. Concordantly, Adh5 deficiency show defective STING-dependent immune responses upon microbial challenge and facilitates viral replication. Thus, cellular oxidative burst-induced RNS attenuates the STING-mediated innate immune responses to microbial infection, while ADH5 licenses STING activation by maintaining cellular SNO homeostasis.https://doi.org/10.1038/s41467-024-46212-z |
| spellingShingle | Mutian Jia Li Chai Jie Wang Mengge Wang Danhui Qin Hui Song Yue Fu Chunyuan Zhao Chengjiang Gao Jihui Jia Wei Zhao S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens Nature Communications |
| title | S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens |
| title_full | S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens |
| title_fullStr | S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens |
| title_full_unstemmed | S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens |
| title_short | S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens |
| title_sort | s nitrosothiol homeostasis maintained by adh5 facilitates sting dependent host defense against pathogens |
| url | https://doi.org/10.1038/s41467-024-46212-z |
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