1. Hepatitis B virus particles activate B cells through the TLR2–MyD88–mTOR axis
- Author
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Hongzhou Lu, Jun Wang, Daniel Hoffmann, Heba Islam, Qian Li, Mengji Lu, Carsten J. Kirschning, and Ulf Dittmer
- Subjects
Pattern recognition receptors ,Cancer Research ,Immunology ,Medizin ,medicine.disease_cause ,Lymphocyte Activation ,Peripheral blood mononuclear cell ,Monocytes ,Article ,Cellular and Molecular Neuroscience ,Mice ,Immune system ,medicine ,Animals ,Hepatitis B Virus, Woodchuck ,lcsh:QH573-671 ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Hepatitis B virus ,Mice, Knockout ,B-Lymphocytes ,biology ,Host Microbial Interactions ,lcsh:Cytology ,TOR Serine-Threonine Kinases ,Woodchuck hepatitis virus ,Pattern recognition receptor ,Cell Biology ,biology.organism_classification ,Hepatitis B ,Virology ,Toll-Like Receptor 2 ,digestive system diseases ,Mice, Inbred C57BL ,TLR2 ,TRIF ,Viral infection ,Myeloid Differentiation Factor 88 ,Biologie - 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.
- Published
- 2021