Department of Dermatology, Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, China; Department of Dermatology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, 222002, China.
Department of Technology, Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, China.
Microb Pathog. 2018 Oct;123:120-125. doi: 10.1016/j.micpath.2018.06.044. Epub 2018 Jun 28.
Autophagy can regulate antimicrobial immunity. However, it is unknown whether autophagy mediates the immune response of dendritic cells (DCs) to Talaromyces marneffei (T. marneffei) infection. Therefore, to explore the relationship between autophagy and multiplication of T. marneffei and investigate whether ERK1/2 signaling pathway regulates activation of autophagy and TNF-α and IFN-γ secretion by intracellular signaling mechanisms during T. marneffei infection in human DCs. DCs were infected with T. marneffei for different times. First, we found that T. marneffei induced activation of autophagy and ERK1/2 in human DCs. Second, the inhibition of ERK1/2 suppressed activation of autophagy in T. marneffei-infected human DCs. Third, the suppression of ERK1/2 and autophagy decreased TNF-α and IFN-γ production and increased the proliferation of T. marneffei. These data suggest that ERK pathway plays vital regulatory roles in activation of autophagy and subsequent cytokine production during T. marneffei infection. Our data further indicate that autophagy is important in the regulation of the DC immune response to T. marneffei infection, thereby extending our understanding of host immune responses to the fungus.
自噬可以调节抗菌免疫。然而,自噬是否介导树突状细胞(DCs)对马尔尼菲青霉(T. marneffei)感染的免疫反应尚不清楚。因此,本研究旨在探讨自噬与马尔尼菲青霉增殖的关系,并研究 ERK1/2 信号通路是否通过细胞内信号机制调节自噬的激活以及 TNF-α和 IFN-γ在人 DC 中分泌,以探讨自噬在 T. marneffei 感染过程中的作用。用 T. marneffei 感染 DC 不同时间。首先,我们发现 T. marneffei 诱导人 DC 中自噬和 ERK1/2 的激活。其次,抑制 ERK1/2 抑制 T. marneffei 感染的人 DC 中自噬的激活。第三,抑制 ERK1/2 和自噬可减少 TNF-α和 IFN-γ的产生并增加 T. marneffei 的增殖。这些数据表明 ERK 通路在 T. marneffei 感染期间自噬的激活和随后细胞因子的产生中发挥重要的调节作用。我们的数据进一步表明,自噬在调节 DC 对 T. marneffei 感染的免疫反应中起重要作用,从而扩展了我们对宿主对真菌免疫反应的理解。