Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection.
Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection.
复制标题
程序性死亡 (PD)-1 缺陷小鼠对鼠型肝炎病毒 3 株 (MHV-3) 感染极其敏感
DOI：
10.1371/journal.ppat.1001347
复制
发表时间：
2011-07
期刊：
影响因子：
6.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Chen Y;Wu S;Guo G;Fei L;Guo S;Yang C;Fu X;Wu Y
The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4+, CD8+ T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy.
登录
查看更多内容
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
DOI：
10.4049/jimmunol.0802041
发表时间：
2009-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fuse S;Tsai CY;Molloy MJ;Allie SR;Zhang W;Yagita H;Usherwood EJ
通讯作者：
Usherwood EJ
影响因子：
7
作者：
Brown KE;Freeman GJ;Wherry EJ;Sharpe AH
通讯作者：
Sharpe AH
DOI：
10.1073/pnas.0809422106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Huang, Xin;Venet, Fabienne;Ayala, Alfred
通讯作者：
Ayala, Alfred
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH