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Abstract：
BACKGROUND: Inactivated parapoxvirus ovis (iPPVO) exerts strong immunomodulatory effects on innate immune cells, making it an attractive therapeutic candidate. However, little is known about the signaling pathways that are involved in iPPVO-induced immune responses.
METHODS: In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling.
RESULTS: We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/β by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling.
CONCLUSIONS: Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species.
METHODS: In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling.
RESULTS: We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/β by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling.
CONCLUSIONS: Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species.
摘要：
背景：灭活卵巢副痘病毒（iPPVO）对先天免疫细胞具有很强的免疫调节作用，使它成为一个有吸引力的治疗候选人。然而,关于iPPVO诱导的免疫反应中涉及的信号通路知之甚少。
方法：在本研究中，我们系统地分析了不同类型的树突状细胞(DC)如何对iPPVO(Zylexis，菌株D1710）通过流式细胞术和ELISA在BALB/c和C57BL/c小鼠中，并通过蛋白质印迹和蛋白质谱分析研究了哪种信号通路与DC活化有关。
结果：我们证明了骨髓来源的常规DCs（BM-cDCs）和骨髓来源的浆细胞样DCs（BM-pDCs）成熟并分泌IFN-α/β，以响应Zylexis刺激两种小鼠品系。同样，Zylexis促进pDC分泌IL-12/23p40和TNF。然而,在BALB/c小鼠中诱导IL-12/23p40和cDC分泌TNF,但在C57BL/6小鼠中不诱导。分析潜在的信号通路显示，iPPVO诱导的cDCs成熟是TLR9独立的，而pDC的成熟部分依赖于TLR9途径。此外，在两种小鼠品系中，cDC产生促炎细胞因子和pDC分泌IFN-α/β部分依赖于TLR9途径。因此,其他信号通路似乎参与DCs对iPPVO的反应，由蛋白质分析支持。
结论：我们的数据为iPPVO传感器的多样性及其在不同菌株和物种之间的不同影响提供了有用的见解。
方法：在本研究中，我们系统地分析了不同类型的树突状细胞(DC)如何对iPPVO(Zylexis，菌株D1710）通过流式细胞术和ELISA在BALB/c和C57BL/c小鼠中，并通过蛋白质印迹和蛋白质谱分析研究了哪种信号通路与DC活化有关。
结果：我们证明了骨髓来源的常规DCs（BM-cDCs）和骨髓来源的浆细胞样DCs（BM-pDCs）成熟并分泌IFN-α/β，以响应Zylexis刺激两种小鼠品系。同样，Zylexis促进pDC分泌IL-12/23p40和TNF。然而,在BALB/c小鼠中诱导IL-12/23p40和cDC分泌TNF,但在C57BL/6小鼠中不诱导。分析潜在的信号通路显示，iPPVO诱导的cDCs成熟是TLR9独立的，而pDC的成熟部分依赖于TLR9途径。此外，在两种小鼠品系中，cDC产生促炎细胞因子和pDC分泌IFN-α/β部分依赖于TLR9途径。因此,其他信号通路似乎参与DCs对iPPVO的反应，由蛋白质分析支持。
结论：我们的数据为iPPVO传感器的多样性及其在不同菌株和物种之间的不同影响提供了有用的见解。
