Although several evidences suggesting the vital roles that innate immunity plays in the persistence and elimination of chronic hepatitis B virus (CHB) infection, the exact mechanism is still complicated. Here, we successfully polarized monocytes derived from healthy human peripheral blood mononuclear cells (PBMCs) into M1/M2 macrophages and detected the effects of hepatitis B core antigen (HBcAg) on the polarization and function of macrophages via the Toll-like receptor (TLR) 2 signaling pathway. The results showed that HBcAg had a negligible impact on M1 polarization, while it effectively impaired M2 polarization and promoted the production of pro-inflammatory cytokines such as IL-6 and TNF-α. Additionally, HBcAg treatment increased TLR2 expression on M2 macrophages and TLR2 blockade abolished the effects of HBcAg on the impaired phenotype and pro-inflammatory cytokine productions of M2 macrophages. Signaling pathway analysis revealed that the nuclear factor κB (NF-κB) pathway, the downstream of TLR2, was upregulated upon HBcAg treatment in both M1 and M2 macrophages. Furthermore, a CD8+ T-macrophage coculture system implied that compared with PBS stimulation, HBcAg-stimulated M2 macrophages regained their ability to activate CD8+ T cells with higher secretion of IFN-γ. Finally, we found impaired expression of M2-related molecules and increased levels of pro-inflammation cytokines in M2 macrophages from CHB patients upon HBcAg stimulation. In conclusion, these results imply a favorable role of HBcAg in the establishment of a pro-inflammatory microenvironment by macrophages, which may suggest a potential therapeutic strategy of HBcAg-induced macrophage activation in CHB infection.

中文翻译：

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乙型肝炎核心抗原削弱极化作用，同时通过TLR2途径促进M2巨噬细胞炎症细胞因子的产生。

尽管有一些证据表明先天免疫在持久性和消除慢性乙型肝炎病毒（CHB）感染中起着至关重要的作用，但确切的机制仍然很复杂。在这里，我们成功地将源自健康人外周血单个核细胞（PBMC）的单核细胞极化为M1 / M2巨噬细胞，并通过Toll样受体（TLR）检测了乙型肝炎核心抗原（HBcAg）对巨噬细胞极化和功能的影响2信号通路。结果表明，HBcAg对M1极化的影响可忽略不计，而它有效削弱了M2极化并促进了促炎细胞因子如IL-6和TNF-α的产生。另外，HBcAg治疗可增加M2巨噬细胞上TLR2的表达，而TLR2阻断则可消除HBcAg对M2巨噬细胞表型受损和促炎性细胞因子产生的影响。信号通路分析表明，M1和M2巨噬细胞中HBcAg处理后，TLR2下游的核因子κB（NF-κB）通路被上调。此外，CD8 + T巨噬细胞共培养系统暗示与PBS刺激相比，HBcAg刺激的M2巨噬细胞恢复了其以更高的IFN-γ分泌激活CD8 + T细胞的能力。最后，我们发现在HBcAg刺激下，来自CHB患者的M2巨噬细胞中M2相关分子的表达受损，促炎细胞因子水平升高。结论，