Abstract

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.

Details

Title
Hepatitis B virus particles activate B cells through the TLR2–MyD88–mTOR axis
Author
Li, Qian 1 ; Wang, Jun 2 ; Islam Heba 3 ; Kirschning Carsten 3 ; Lu Hongzhou 4 ; Hoffmann, Daniel 5 ; Dittmer Ulf 6 ; Lu Mengji 6 

 University Hospital of Essen, University of Duisburg-Essen, Institute of Virology, Essen, Germany; Shanghai Public Health Clinical Center, Department of Infectious Diseases, Shanghai, China (GRID:grid.470110.3) (ISNI:0000 0004 1770 0943) 
 University Hospital of Essen, University of Duisburg-Essen, Institute of Virology, Essen, Germany (GRID:grid.470110.3); The Fifth People’s Hospital of Wuxi, Jiangnan University, Center of Clinical Laboratory, Wuxi, China (GRID:grid.258151.a) (ISNI:0000 0001 0708 1323); Bioinformatics and Computational Biophysics, University of Duisburg-Essen, Essen, Germany (GRID:grid.5718.b) (ISNI:0000 0001 2187 5445) 
 University Hospital of Essen, University of Duisburg-Essen, Institute of Medical Microbiology, Essen, Germany (GRID:grid.5718.b) 
 Shanghai Public Health Clinical Center, Department of Infectious Diseases, Shanghai, China (GRID:grid.470110.3) (ISNI:0000 0004 1770 0943) 
 Bioinformatics and Computational Biophysics, University of Duisburg-Essen, Essen, Germany (GRID:grid.5718.b) (ISNI:0000 0001 2187 5445) 
 University Hospital of Essen, University of Duisburg-Essen, Institute of Virology, Essen, Germany (GRID:grid.5718.b) 
Publication year
2021
Publication date
Jan 2021
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2476049426
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.