Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models
Toll-like receptors (TLRs) play a crucial role in activation of innate immunity, which is essential for inducing effective adaptive immune responses. Our previous studies have shown that toll-like receptor 2 (TLR2) is required to induce effective virus-specific T-cell responses against hepatitis B v...
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01495/full |
| _version_ | 1818909802783309824 |
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| author | Yong Lin Yong Lin Yong Lin Xuan Huang Xuan Huang Jun Wu Jia Liu Jia Liu Mingfa Chen Zhiyong Ma Ejuan Zhang Yan Liu Shunmei Huang Qian Li Xiaoyong Zhang Jinlin Hou Dongliang Yang Mengji Lu Mengji Lu Yang Xu |
| author_facet | Yong Lin Yong Lin Yong Lin Xuan Huang Xuan Huang Jun Wu Jia Liu Jia Liu Mingfa Chen Zhiyong Ma Ejuan Zhang Yan Liu Shunmei Huang Qian Li Xiaoyong Zhang Jinlin Hou Dongliang Yang Mengji Lu Mengji Lu Yang Xu |
| author_sort | Yong Lin |
| collection | DOAJ |
| description | Toll-like receptors (TLRs) play a crucial role in activation of innate immunity, which is essential for inducing effective adaptive immune responses. Our previous studies have shown that toll-like receptor 2 (TLR2) is required to induce effective virus-specific T-cell responses against hepatitis B virus (HBV) in vivo. However, the contribution of TLR2 activation to adaptive immunity and HBV clearance remains to be clarified. In this study, we explored the hydrodynamic injection (HI) mouse models for HBV infection and examined how the TLR2 agonist Pam3CSK (P3C) influences HBV control and modulates HBV-specific T-cell response if applied in vivo. We found that TLR2 activation by P3C injection leads to the rapid but transient production of serum proinflammatory factors interleukin-6 and tumor necrosis factor-α and activation of CD8+ T cells in vivo. Then, the anti-HBV effect and HBV-specific T-cell immunity were investigated by TLR2 activation in the mouse models for persistent or acute HBV infections using HBV plasmids pAAV-HBV1.2 and pSM2, respectively. Both P3C application at early stage and pre-activation promoted HBV clearance, while only TLR2 pre-activation enhanced HBV-specific T-cell response in the liver. In the mouse model for acute HBV infection, P3C application had no significant effect on HBV clearance though P3C significantly enhanced the HBV-specific T-cell response. Collectively, TLR2 pre-activation enhances HBV-specific T-cell responses and accelerates HBV clearance in HI mouse models. Thus, the modulation of host immune status by TLR2 agonists may be explored for immunotherapeutic strategies to control HBV infection. |
| first_indexed | 2024-12-19T22:32:42Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T22:32:42Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-f584cfa8281245abae4e493ce93d14e32022-12-21T20:03:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01495367190Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse ModelsYong Lin0Yong Lin1Yong Lin2Xuan Huang3Xuan Huang4Jun Wu5Jia Liu6Jia Liu7Mingfa Chen8Zhiyong Ma9Ejuan Zhang10Yan Liu11Shunmei Huang12Qian Li13Xiaoyong Zhang14Jinlin Hou15Dongliang Yang16Mengji Lu17Mengji Lu18Yang Xu19Department of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Virology, University Hospital of Essen, Essen, GermanyDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Virology, University Hospital of Essen, Essen, GermanyState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Virology, University Hospital of Essen, Essen, GermanyDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Virology, University Hospital of Essen, Essen, GermanyMucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaDepartment of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Virology, University Hospital of Essen, Essen, GermanyState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Virology, University Hospital of Essen, Essen, GermanyDepartment of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaToll-like receptors (TLRs) play a crucial role in activation of innate immunity, which is essential for inducing effective adaptive immune responses. Our previous studies have shown that toll-like receptor 2 (TLR2) is required to induce effective virus-specific T-cell responses against hepatitis B virus (HBV) in vivo. However, the contribution of TLR2 activation to adaptive immunity and HBV clearance remains to be clarified. In this study, we explored the hydrodynamic injection (HI) mouse models for HBV infection and examined how the TLR2 agonist Pam3CSK (P3C) influences HBV control and modulates HBV-specific T-cell response if applied in vivo. We found that TLR2 activation by P3C injection leads to the rapid but transient production of serum proinflammatory factors interleukin-6 and tumor necrosis factor-α and activation of CD8+ T cells in vivo. Then, the anti-HBV effect and HBV-specific T-cell immunity were investigated by TLR2 activation in the mouse models for persistent or acute HBV infections using HBV plasmids pAAV-HBV1.2 and pSM2, respectively. Both P3C application at early stage and pre-activation promoted HBV clearance, while only TLR2 pre-activation enhanced HBV-specific T-cell response in the liver. In the mouse model for acute HBV infection, P3C application had no significant effect on HBV clearance though P3C significantly enhanced the HBV-specific T-cell response. Collectively, TLR2 pre-activation enhances HBV-specific T-cell responses and accelerates HBV clearance in HI mouse models. Thus, the modulation of host immune status by TLR2 agonists may be explored for immunotherapeutic strategies to control HBV infection.https://www.frontiersin.org/article/10.3389/fimmu.2018.01495/fulltoll-like receptor 2hepatitis B virusmouse modelproinflammatory cytokinesT-cell immunity |
| spellingShingle | Yong Lin Yong Lin Yong Lin Xuan Huang Xuan Huang Jun Wu Jia Liu Jia Liu Mingfa Chen Zhiyong Ma Ejuan Zhang Yan Liu Shunmei Huang Qian Li Xiaoyong Zhang Jinlin Hou Dongliang Yang Mengji Lu Mengji Lu Yang Xu Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models Frontiers in Immunology toll-like receptor 2 hepatitis B virus mouse model proinflammatory cytokines T-cell immunity |
| title | Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models |
| title_full | Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models |
| title_fullStr | Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models |
| title_full_unstemmed | Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models |
| title_short | Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models |
| title_sort | pre activation of toll like receptor 2 enhances cd8 t cell responses and accelerates hepatitis b virus clearance in the mouse models |
| topic | toll-like receptor 2 hepatitis B virus mouse model proinflammatory cytokines T-cell immunity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01495/full |
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