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

Affiliation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Li, Qian;
Affiliation
Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Affiliated Hospital of Jiangnan University, Wuxi, China.
Yan, Yan;
Affiliation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Liu, Jia;
Affiliation
Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Huang, Xuan;
Affiliation
Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Zhang, Xiaoyong;
GND
114777020
LSF
51943
Affiliation
Institute of Medical Microbiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Kirschning, Carsten;
Affiliation
Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Xu, Haifeng C;
Affiliation
Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Lang, Philipp A.;
LSF
47363
Affiliation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Dittmer, Ulf;
Affiliation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Zhang, Ejuan;
GND
1145674135
LSF
16040
Affiliation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Lu, Mengji

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.

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Citation style:
Li, Q., Yan, Y., Liu, J., Huang, X., Zhang, X., Kirschning, C.J., Xu, H.C., Lang, P.A., Dittmer, U., Zhang, E., Lu, M., 2019. Toll-Like Receptor 7 Activation Enhances CD8+ T Cell Effector Functions by Promoting Cellular Glycolysis. https://doi.org/10.3389/fimmu.2019.02191
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