| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Yin, Wenwei Xu, Long Lian, Zhexiong Tian, Zhigang Li, Min Wei, Haiming Zheng, Xiaodong Sun, Rui Chen, Yongyan |
| Description |
Author Affiliation: Li M ( Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China); Sun R ( Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China); Xu L ( Institute of Immunology and Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.); Yin W ( Institute of Immunology and Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.); Chen Y ( Institute of Immunology and Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.); Zheng X ( Institute of Immunology and Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.); Lian Z ( Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China); Wei H ( Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China); Tian Z ( Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China) |
| Abstract |
Hepatitis B virus (HBV) persistence is a fundamental process in chronic HBV infection and a key factor in all related liver diseases; however, the mechanisms have yet to be elucidated. We studied the role of TLR2 in HBV persistence using a well-established HBV-carrier mouse model generated by hydrodynamically injecting a phospho-adeno-associated virus/HBV1.2 plasmid into mice. We found that a genetic deficiency in TLR2 improves HBV elimination, whereas activating TLR2 led to more stable HBV persistence, suggesting that TLR2 activation is critical in HBV persistence. Furthermore, we noted that TLR2 activation could inhibit CD8(+) T cell function, causing the exhaustion phenotype in HBV-carrier mice, because TLR2 deficiency might rescue CD8(+) T cell function in a cellular adoptive experiment. TLR2 expression on Kupffer cells (KCs) was upregulated in HBV-carrier mice, which accounts for HBV persistence, because the difference in anti-HBV immunity between HBV-carrier wild-type and Tlr2(-/-) mice did not exist after KC depletion. In addition, similar to TLR2 deficiency, after KC depletion, CD8(+) T cells were more efficiently activated in HBV-carrier mice, leading to rapid HBV elimination. KCs produced more IL-10 upon TLR2 activation in response to direct hepatitis B core Ag stimulation, and the elevated IL-10 inhibited CD8(+) T cell function in HBV-carrier mice, because IL-10 deficiency or anti-IL-10R treatment resulted in CD8(+) T cells with stronger antiviral function. In conclusion, KCs support liver tolerance by inducing anti-HBV CD8(+) T cell exhaustion via IL-10 production after TLR2 activation by hepatitis B core Ag stimulation. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
7 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-10-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cd8-positive T-lymphocytes Immunology Carrier State Hepatitis B Core Antigens Hepatitis B, Chronic Interleukin-10 Kupffer Cells Toll-like Receptor 2 Animals Bone Marrow Cells Virology Disease Models, Animal Enzyme Activation Genetics Hepatitis B Virus Biosynthesis Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Knockout Receptors, Interleukin-10 Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
