Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models

Frontiers in Immunology
Yong LinYang Xu

Abstract

Toll-like receptors (TLRs) play a crucial role in activation of innate immunity, which is essential for inducing effective adaptive immune responses. Our previous studies have shown that toll-like receptor 2 (TLR2) is required to induce effective virus-specific T-cell responses against hepatitis B virus (HBV) in vivo. However, the contribution of TLR2 activation to adaptive immunity and HBV clearance remains to be clarified. In this study, we explored the hydrodynamic injection (HI) mouse models for HBV infection and examined how the TLR2 agonist Pam3CSK (P3C) influences HBV control and modulates HBV-specific T-cell response if applied in vivo. We found that TLR2 activation by P3C injection leads to the rapid but transient production of serum proinflammatory factors interleukin-6 and tumor necrosis factor-α and activation of CD8+ T cells in vivo. Then, the anti-HBV effect and HBV-specific T-cell immunity were investigated by TLR2 activation in the mouse models for persistent or acute HBV infections using HBV plasmids pAAV-HBV1.2 and pSM2, respectively. Both P3C application at early stage and pre-activation promoted HBV clearance, while only TLR2 pre-activation enhanced HBV-specific T-cell response in the liver. In the mouse mod...Continue Reading

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Citations

Oct 23, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ejuan ZhangMengji Lu
Aug 8, 2020·Scandinavian Journal of Immunology·Sonal YadavManisha Yadav
Oct 21, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yu LiuXiufang Weng
Jul 5, 2021·Journal of Gastroenterology·Yan YanChantsalmaa Davgadorj
Jan 13, 2022·Viral Immunology·Maryam NaghibMohammad Kazemi Arababadi

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Datasets Mentioned

BETA
V01460
AY220698.1

Methods Mentioned

BETA
PCR
ELISA
Flow Cytometry
FACS
ELISAs
antibody assay

Software Mentioned

GraphPad
FlowJo
GraphPad Prism

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