PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS
Although it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocy...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02609/full |
| _version_ | 1798044898122792960 |
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| author | Cennan Yin Chenyun Wu Xinyue Du Yan Fang Juebiao Pu Jianhua Wu Lili Tang Wei Zhao Yongqiang Weng Xiaokui Guo Guangjie Chen Zhaojun Wang |
| author_facet | Cennan Yin Chenyun Wu Xinyue Du Yan Fang Juebiao Pu Jianhua Wu Lili Tang Wei Zhao Yongqiang Weng Xiaokui Guo Guangjie Chen Zhaojun Wang |
| author_sort | Cennan Yin |
| collection | DOAJ |
| description | Although it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocyte bactericidal activity. PRL2 (Phosphatase Regenerating Liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation. in vitro experiments showed that PRL2 was sensitive to hydrogen peroxide (H2O2), a common damage signal at inflamed sites. In response to infection, PRL2 knockout (KO) phagocytes were hyper activated, produced more reactive oxygen species (ROS) and exhibited enhanced bactericidal activity. Mice with PRL2 deficiency in the myeloid cell compartment were resistant to lethal listeria infection and cleared the bacteria more rapidly and effectively. Moreover, in vitro experiments demonstrated that PRL2 binds to GTPase Rac and regulates ROS production. Rac GTPases were more active in PRL2 (KO) phagocytes than in wild type cells after bacterium infection. Our findings indicate that PRL2 senses ROS at inflamed sites and regulates ROS production in phagocytes. This positive feedback mechanism promotes bactericidal activity of phagocytes and may play an important role in innate anti-bacterial immunity. |
| first_indexed | 2024-04-11T23:11:56Z |
| format | Article |
| id | doaj.art-675b052de37c4ecbbd797f5b864266d5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T23:11:56Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-675b052de37c4ecbbd797f5b864266d52022-12-22T03:57:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02609414783PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROSCennan Yin0Chenyun Wu1Xinyue Du2Yan Fang3Juebiao Pu4Jianhua Wu5Lili Tang6Wei Zhao7Yongqiang Weng8Xiaokui Guo9Guangjie Chen10Zhaojun Wang11Department of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Basic Medicine, Guangxi Medical University, Nanning, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaAlthough it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocyte bactericidal activity. PRL2 (Phosphatase Regenerating Liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation. in vitro experiments showed that PRL2 was sensitive to hydrogen peroxide (H2O2), a common damage signal at inflamed sites. In response to infection, PRL2 knockout (KO) phagocytes were hyper activated, produced more reactive oxygen species (ROS) and exhibited enhanced bactericidal activity. Mice with PRL2 deficiency in the myeloid cell compartment were resistant to lethal listeria infection and cleared the bacteria more rapidly and effectively. Moreover, in vitro experiments demonstrated that PRL2 binds to GTPase Rac and regulates ROS production. Rac GTPases were more active in PRL2 (KO) phagocytes than in wild type cells after bacterium infection. Our findings indicate that PRL2 senses ROS at inflamed sites and regulates ROS production in phagocytes. This positive feedback mechanism promotes bactericidal activity of phagocytes and may play an important role in innate anti-bacterial immunity.https://www.frontiersin.org/article/10.3389/fimmu.2018.02609/fullPRL2oxidative burstbactericidal activityRac GTPaseneutrophilmacrophage |
| spellingShingle | Cennan Yin Chenyun Wu Xinyue Du Yan Fang Juebiao Pu Jianhua Wu Lili Tang Wei Zhao Yongqiang Weng Xiaokui Guo Guangjie Chen Zhaojun Wang PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS Frontiers in Immunology PRL2 oxidative burst bactericidal activity Rac GTPase neutrophil macrophage |
| title | PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS |
| title_full | PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS |
| title_fullStr | PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS |
| title_full_unstemmed | PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS |
| title_short | PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS |
| title_sort | prl2 controls phagocyte bactericidal activity by sensing and regulating ros |
| topic | PRL2 oxidative burst bactericidal activity Rac GTPase neutrophil macrophage |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02609/full |
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