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The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model.

ABSTRACT: The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model. Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice (WT) and a panel of mouse strains lacking specific innate immunity component expression. We found higher levels of HBV protein production and replication in Tlr2-/-, Tlr23479-/-, 3d/Tlr24-/-, Myd88/Trif-/- and Irak4-/- mice, which was associated with reduced HBV-specific CD8+ T-cell responses in these mice. Importantly, HBV clearance was delayed for more than 2 weeks in 3d/Tlr24-/-, Myd88/Trif-/- and Irak4-/- mice compared to WT mice. HBV-specific CD8+ T-cell responses were functionally impaired for producing the cytokines IFN-?, TNF-? and IL-2 in TLR signaling-deficient mice compared to WT mice. In conclusion, the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8+ T-cell responses.

SUBMITTER: Ma Z

PROVIDER: S-EPMC5719144 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The IL-1R/TLR signaling pathway is essential for efficient CD8<sup>+</sup> T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model.

Ma Zhiyong Z Liu Jia J Wu Weimin W Zhang Ejuan E Zhang Xiaoyong X Li Qian Q Zelinskyy Gennadiy G Buer Jan J Dittmer Ulf U Kirschning Carsten J CJ Lu Mengji M

Cellular & molecular immunology 20170731 12

The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse mod ...[more]

PMID: 28757610

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Project description:BACKGROUND: Development in systems biology research has accelerated in recent years, and the reconstructions for molecular networks can provide a global view to enable in-depth investigation on numerous system properties in biology. However, we still lack a systematic approach to reconstruct the dynamic protein-protein association networks at different time stages from high-throughput data to further analyze the possible cross-talks among different signaling/regulatory pathways. METHODS: In this study we integrated protein-protein interactions from different databases to construct the rough protein-protein association networks (PPANs) during TNFalpha-induced inflammation. Next, the gene expression profiles of TNFalpha-induced HUVEC and a stochastic dynamic model were used to rebuild the significant PPANs at different time stages, reflecting the development and progression of endothelium inflammatory responses. A new cross-talk ranking method was used to evaluate the potential core elements in the related signaling pathways of toll-like receptor 4 (TLR-4) as well as receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R). RESULTS: The highly ranked cross-talks which are functionally relevant to the TNFalpha pathway were identified. A bow-tie structure was extracted from these cross-talk pathways, suggesting the robustness of network structure, the coordination of signal transduction and feedback control for efficient inflammatory responses to different stimuli. Further, several characteristics of signal transduction and feedback control were analyzed. CONCLUSIONS: A systematic approach based on a stochastic dynamic model is proposed to generate insight into the underlying defense mechanisms of inflammation via the construction of corresponding signaling networks upon specific stimuli. In addition, this systematic approach can be applied to other signaling networks under different conditions in different species. The algorithm and method proposed in this study could expedite prospective systems biology research when better experimental techniques for protein expression detection and microarray data with multiple sampling points become available in the future.

Dataset Information

The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model.

Publications

The IL-1R/TLR signaling pathway is essential for efficient CD8<sup>+</sup> T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model.

Similar Datasets

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