Activation of the TLR signaling pathway in CD8+ T cells counteracts liver endothelial cell-induced T cell tolerance
Zhang, E., Yan, H., Li, Q. et al.The Toll-like receptor (TLR) signaling pathway, which is composed of a group of highly conserved molecules, plays a critical role in the recognition of pathogen-associated molecular patterns (PAMPs). Innate immunity activated through the TLR signaling pathway serves as a first defense against infectious diseases. However, the exact function of TLR signaling in viral infections remains to be elucidated. Previously, a number of clinical reports indicated that TLR expression and function are impaired in chronic hepatitis B virus (HBV) infection. A specific question was raised regarding whether deficient TLR function may contribute to chronic HBV infection, characterized by low or absent T cell responses against HBV. In our previous study published in Cellular and Molecular Immunology, Ma et al. demonstrated that deficiency in TLRs or adaptor molecules (MyD88/Trif or IRAK4) resulted in not only elevated expression of HBsAg and HBV DNA but also delayed HBV clearance in the hydrodynamic injection HBV mouse model. HBV-specific T cell responses, which play a key role in HBV control and clearance, were detectable but functionally impaired in IL-1R/TLR deficient mice. This study highlighted the essential role of the IL-1R/TLR signaling pathway in adaptive immunity and HBV clearance in vivo. This finding suggested that TLR deficiency may be involved in the low HBV-specific T cell responses observed during chronic HBV infection in humans.
Zhang, E., Yan, H., Li, Q. et al. "Activation of the TLR signaling pathway in CD8+ T cells counteracts liver endothelial cell-induced T cell tolerance" Cellular & Molecular Immunology (2019): doi: 10.1038/s41423-019-0255-8