Hepatitis B virus particles activate B cells through the TLR2–MyD88–mTOR axis

GND
1209705869
Zugehörige Organisation
Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
Li, Qian;
GND
1248950712
Zugehörige Organisation
Bioinformatics and Computational Biophysics, University of Duisburg-Essen, Essen, Germany
Wang, Jun;
Zugehörige Organisation
Institute of Medical Microbiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Islam, Heba;
GND
114777020
LSF
51943
Zugehörige Organisation
Institute of Medical Microbiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Kirschning, Carsten;
Zugehörige Organisation
Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
Lu, Hongzhou;
GND
1021044180
ORCID
0000-0003-2973-7869
LSF
16263
Zugehörige Organisation
Bioinformatics and Computational Biophysics, University of Duisburg-Essen, Essen, Germany
Hoffmann, Daniel;
GND
1201144469
LSF
47363
Zugehörige Organisation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Dittmer, Ulf;
GND
1145674135
LSF
16040
Zugehörige Organisation
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Lu, Mengji
Host immune control plays a pivotal role in resolving primary hepatitis-B-virus (HBV) infections. The complex interaction between HBV and host immune cells, however, remains unclear. In this study, the transcriptional profiling of specimens from animals infected with woodchuck hepatitis virus (WHV) indicated TLR2 mRNA accumulation as most strongly impacted during WHV infection resolution as compared to other mRNAs. Analysis of blood transcriptional modules demonstrated that monocytes and B-cells were the predominantly activated cell types in animals that showed resolution of infection, which was similar to the response of TLR2-stimulated PBMCs. Further investigation of TLR2-stimulated B-cells pointed at interactions between activated TLR signaling, Akt-mTOR, and glucose metabolic pathways. Moreover, analysis of B-cells from Tlr2−/− , Trif−/− , Myd88−/− , and Trif/Myd88−/− mice challenged with HBV particles indicated B-cell function and glucose metabolism alterations is TLR2-MyD88-mTOR axis dependent. Overall, our study implicates B-cell TLR2 activation in HBV infection resolution.

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