Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses
Summary: Recognition of the components of Mycobacterium tuberculosis (Mtb) by macrophages is vital for initiating a cascade of host immune responses. However, the recognition of Mtb-secretory proteins by the receptor-independent pathways of the host remains unclear. Rv1804c is a highly conserved sec...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224003225 |
| _version_ | 1797304438712434688 |
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| author | Jianjian Zheng Chunsheng Dong Sidong Xiong |
| author_facet | Jianjian Zheng Chunsheng Dong Sidong Xiong |
| author_sort | Jianjian Zheng |
| collection | DOAJ |
| description | Summary: Recognition of the components of Mycobacterium tuberculosis (Mtb) by macrophages is vital for initiating a cascade of host immune responses. However, the recognition of Mtb-secretory proteins by the receptor-independent pathways of the host remains unclear. Rv1804c is a highly conserved secretory protein in Mtb. However, its exact function and underlying mechanism in Mtb infection remain poorly understood. In the present study, we observed that Rv1804c activates macrophage-mediated proinflammatory responses in an IKKα-independent manner. Furthermore, we noted that Rv1804c inhibits mycobacterial survival. By elucidating the underlying mechanisms, we observed that Rv1804c activates IκBα by directly interacting with its PEST domain. Moreover, Rv1804c was enriched in attenuated but not in virulent mycobacteria and associated with the disease process of tuberculosis. Our findings provide an alternative pathway via which a mycobacterial secretory protein activates macrophage-mediated proinflammatory responses. Our study findings may shed light on the prevention and treatment of tuberculosis. |
| first_indexed | 2024-03-08T00:09:31Z |
| format | Article |
| id | doaj.art-c70f4f2edc1647dbaa1458be1976ef26 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T00:09:31Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-c70f4f2edc1647dbaa1458be1976ef262024-02-17T06:42:03ZengElsevieriScience2589-00422024-03-01273109101Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responsesJianjian Zheng0Chunsheng Dong1Sidong Xiong2Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China; Corresponding authorJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China; Corresponding authorSummary: Recognition of the components of Mycobacterium tuberculosis (Mtb) by macrophages is vital for initiating a cascade of host immune responses. However, the recognition of Mtb-secretory proteins by the receptor-independent pathways of the host remains unclear. Rv1804c is a highly conserved secretory protein in Mtb. However, its exact function and underlying mechanism in Mtb infection remain poorly understood. In the present study, we observed that Rv1804c activates macrophage-mediated proinflammatory responses in an IKKα-independent manner. Furthermore, we noted that Rv1804c inhibits mycobacterial survival. By elucidating the underlying mechanisms, we observed that Rv1804c activates IκBα by directly interacting with its PEST domain. Moreover, Rv1804c was enriched in attenuated but not in virulent mycobacteria and associated with the disease process of tuberculosis. Our findings provide an alternative pathway via which a mycobacterial secretory protein activates macrophage-mediated proinflammatory responses. Our study findings may shed light on the prevention and treatment of tuberculosis.http://www.sciencedirect.com/science/article/pii/S2589004224003225ImmunologyMicrobiology |
| spellingShingle | Jianjian Zheng Chunsheng Dong Sidong Xiong Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses iScience Immunology Microbiology |
| title | Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses |
| title_full | Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses |
| title_fullStr | Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses |
| title_full_unstemmed | Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses |
| title_short | Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses |
| title_sort | mycobacterial rv1804c binds to the pest domain of iκbα and activates macrophage mediated proinflammatory responses |
| topic | Immunology Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224003225 |
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