Department of Biological Systems Engineering, College of Agriculture and Life Sciences & College of Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
Viruses. 2023 May 19;15(5):1198. doi: 10.3390/v15051198.
Interferon-γ (IFN-γ) is a cytokine that plays an important role in immune regulation, especially in the activation and differentiation of immune cells. Toll-like receptors (TLRs) are a family of pattern-recognition receptors that sense structural motifs related to pathogens and alert immune cells to the invasion. Both IFN-γ and TLR agonists have been used as immunoadjuvants to augment the efficacy of cancer immunotherapies and vaccines against infectious diseases or psychoactive compounds. In this study, we aimed to explore the potential of IFN-γ and TLR agonists being applied simultaneously to boost dendritic cell activation and the subsequent antigen presentation. In brief, murine dendritic cells were treated with IFN-γ and/or the TLR agonists, polyinosinic-polycytidylic acid (poly I:C), or resiquimod (R848). Next, the dendritic cells were stained for an activation marker, a cluster of differentiation 86 (CD86), and the percentage of CD86-positive cells was measured by flow cytometry. From the cytometric analysis, IFN-γ efficiently stimulated a considerable number of the dendritic cells, while the TLR agonists by themselves could merely activate a few compared to the control. The combination of IFN-γ with poly I:C or R848 triggered a higher amount of dendritic cell activation than IFN-γ alone. For instance, 10 ng/mL IFN-γ with 100 µg/mL poly I:C achieved 59.1% cell activation, which was significantly higher than the 33.4% CD86-positive cells obtained by 10 ng/mL IFN-γ. These results suggested that IFN-γ and TLR agonists could be applied as complementary systems to promote dendritic cell activation and antigen presentation. There might be a synergy between the two classes of molecules, but further investigation is warranted to ascertain the interaction of their promotive activities.
干扰素-γ(IFN-γ)是一种细胞因子,在免疫调节中发挥重要作用,尤其是在免疫细胞的激活和分化方面。Toll 样受体(TLRs)是一类模式识别受体,能够识别与病原体相关的结构基序,并向免疫细胞发出入侵警报。IFN-γ 和 TLR 激动剂都已被用作免疫佐剂,以增强癌症免疫疗法和针对传染病或精神活性化合物的疫苗的疗效。在这项研究中,我们旨在探讨同时应用 IFN-γ 和 TLR 激动剂来增强树突状细胞激活和随后的抗原呈递的潜力。简而言之,用 IFN-γ 和/或 TLR 激动剂聚肌苷酸-聚胞苷酸(poly I:C)或瑞喹莫德(R848)处理小鼠树突状细胞。然后,用流式细胞术对树突状细胞进行激活标志物(CD86)染色,并测量 CD86 阳性细胞的百分比。从细胞计量分析中可以看出,IFN-γ 有效地刺激了相当数量的树突状细胞,而 TLR 激动剂本身与对照相比只能激活少数树突状细胞。IFN-γ 与 poly I:C 或 R848 联合使用可引发比单独使用 IFN-γ 更高水平的树突状细胞激活。例如,10ng/mL IFN-γ 与 100μg/mL poly I:C 可达到 59.1%的细胞激活率,明显高于 10ng/mL IFN-γ 获得的 33.4%CD86 阳性细胞。这些结果表明,IFN-γ 和 TLR 激动剂可作为互补系统应用,以促进树突状细胞激活和抗原呈递。这两类分子之间可能存在协同作用,但需要进一步研究以确定它们的促进活性的相互作用。
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