Toll-Like Receptor 7 Activation Enhances CD8+ T Cell Effector Functions by Promoting Cellular Glycolysis

Frontiers in Immunology

Yan Yan¹  Jia Liu²  Haifeng C. Xu³  Philipp A. Lang³  Xiaoyong Zhang⁴  Xuan Huang⁴  Carsten Kirschning⁵  Ulf Dittmer⁶  Qian Li⁶  Mengji Lu⁶  Ejuan Zhang⁷ 

[1] Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Affiliated Hospital of Jiangnan University, Wuxi, China;Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany;Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China;Institute of Medical Microbiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany;Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany;Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China;

关键词: toll-like receptor 7;    CD8+ T cells;    PI3K-Akt-mTOR;    glycolysis;    IRF4;   

DOI  :  10.3389/fimmu.2019.02191

来源: DOAJ

【 摘 要 】

The activation of TLR7 signaling in T cells accelerates antigen-specific responses. Such responses play an essential role in eliminating viral infections and can be anti-tumorigenic. However, the underlying mechanisms of how TLR7 can promote the optimal function of CD8+ T cells remain unclear. To investigate how TLR signaling directly contributes to CD8+ T cell functions, we examine the activation of cellular TLR7-related pathways and functional and metabolic alterations in TLR7-stimulated T cells during T cell receptor (TCR) signaling. In the present study, we investigated the activation of CD8+ T cells in response to direct stimulation by TLR7 ligands. TLR7 stimulation could promote the effector functions of purified CD8+ T cells in vitro. The TLR7-induced activation of CD8+ T cells occurs if CD8+ T cells were primed by αCD3 activation and increasingly expressed TLR7. MyD88 and AKT-mTOR signaling plays a critical role in TLR7-induced T cell activation. In addition to the upregulation of immune-related genes, metabolic alterations in CD8+ T cells, including the upregulation of glucose uptake and glycolysis, occurred by TLR7 stimulation. Glycolysis was found to be regulated by the AKT-mTOR pathway and a downstream transcription factor IRF4. Blocking glycolysis by either direct glucose deprivation or modulating the mTOR pathway and IRF4 expression was found to impair T cell activation and functions. Taken together, the activation of TLR7 signaling promotes the effector functions of CD8+ T cells by enhancing cellular glycolysis.

【 授权许可】

Unknown