Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages
Tuberculosis (TB) remains the major cause of mortality and morbidity, causing approximately 1.3 million deaths annually. As a highly successful pathogen, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) has evolved numerous strategies to evade host immune responses, making it e...
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2025-01-01
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| author | Reziya Wumaier Ke Zhang Jing Zhou Zilu Wen Zihan Chen Geyang Luo Hao Wang Juliang Qin Bing Du Hua Ren Yanzheng Song Qian Gao Bo Yan |
| author_facet | Reziya Wumaier Ke Zhang Jing Zhou Zilu Wen Zihan Chen Geyang Luo Hao Wang Juliang Qin Bing Du Hua Ren Yanzheng Song Qian Gao Bo Yan |
| author_sort | Reziya Wumaier |
| collection | DOAJ |
| description | Tuberculosis (TB) remains the major cause of mortality and morbidity, causing approximately 1.3 million deaths annually. As a highly successful pathogen, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) has evolved numerous strategies to evade host immune responses, making it essential to understand the interactions between <i>Mtb</i> and host cells. G-protein-coupled receptor 84 (GPR84), a member of the G-protein-coupled receptor family, contributes to the regulation of pro-inflammatory reactions and the migration of innate immune cells, such as macrophages. Its role in mycobacterial infection, however, has not yet been explored. We found that GPR84 is induced in whole blood samples from tuberculosis patients and <i>Mycobacterium marinum (Mm</i>)-infected macrophage models. Using a <i>Mm-wasabi</i> infection model in mouse tails, we found that GPR84 is an important determinant of the extent of tissue damage. Furthermore, from our studies in an in vitro macrophage <i>Mm</i> infection model, it appears that GPR84 inhibits pro-inflammatory cytokines expression and increases intracellular lipid droplet (LD) accumulation, thereby promoting intracellular bacterial survival. Our findings suggest that GPR84 could be a potential therapeutic target for host-directed anti-TB therapeutics. |
| format | Article |
| id | doaj-art-9abddfd56e1a46989bed5457fe24112d |
| institution | Kabale University |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-9abddfd56e1a46989bed5457fe24112d2025-01-24T13:42:41ZengMDPI AGMicroorganisms2076-26072025-01-0113111010.3390/microorganisms13010110Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in MacrophagesReziya Wumaier0Ke Zhang1Jing Zhou2Zilu Wen3Zihan Chen4Geyang Luo5Hao Wang6Juliang Qin7Bing Du8Hua Ren9Yanzheng Song10Qian Gao11Bo Yan12Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Public Health Clinical Center, Fudan University, Shanghai 200433, ChinaShanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Public Health Clinical Center, Fudan University, Shanghai 200433, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaTuberculosis (TB) remains the major cause of mortality and morbidity, causing approximately 1.3 million deaths annually. As a highly successful pathogen, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) has evolved numerous strategies to evade host immune responses, making it essential to understand the interactions between <i>Mtb</i> and host cells. G-protein-coupled receptor 84 (GPR84), a member of the G-protein-coupled receptor family, contributes to the regulation of pro-inflammatory reactions and the migration of innate immune cells, such as macrophages. Its role in mycobacterial infection, however, has not yet been explored. We found that GPR84 is induced in whole blood samples from tuberculosis patients and <i>Mycobacterium marinum (Mm</i>)-infected macrophage models. Using a <i>Mm-wasabi</i> infection model in mouse tails, we found that GPR84 is an important determinant of the extent of tissue damage. Furthermore, from our studies in an in vitro macrophage <i>Mm</i> infection model, it appears that GPR84 inhibits pro-inflammatory cytokines expression and increases intracellular lipid droplet (LD) accumulation, thereby promoting intracellular bacterial survival. Our findings suggest that GPR84 could be a potential therapeutic target for host-directed anti-TB therapeutics.https://www.mdpi.com/2076-2607/13/1/110tuberculosis (TB)G-protein-coupled receptors 84 (GPR84)pro-inflammatory cytokines |
| spellingShingle | Reziya Wumaier Ke Zhang Jing Zhou Zilu Wen Zihan Chen Geyang Luo Hao Wang Juliang Qin Bing Du Hua Ren Yanzheng Song Qian Gao Bo Yan Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages Microorganisms tuberculosis (TB) G-protein-coupled receptors 84 (GPR84) pro-inflammatory cytokines |
| title | Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages |
| title_full | Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages |
| title_fullStr | Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages |
| title_full_unstemmed | Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages |
| title_short | Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages |
| title_sort | mycobacteria exploit host gpr84 to dampen pro inflammatory responses and promote infection in macrophages |
| topic | tuberculosis (TB) G-protein-coupled receptors 84 (GPR84) pro-inflammatory cytokines |
| url | https://www.mdpi.com/2076-2607/13/1/110 |
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