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感染华支睾吸虫幼虫的小鼠中特定细胞反应和细胞因子表达谱的动态变化。

The dynamics of select cellular responses and cytokine expression profiles in mice infected with juvenile Clonorchis sinensis.

机构信息

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun, China; College of Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun, China.

出版信息

Acta Trop. 2021 May;217:105852. doi: 10.1016/j.actatropica.2021.105852. Epub 2021 Feb 3.

DOI:10.1016/j.actatropica.2021.105852
PMID:33548205
Abstract

Clonorchiasis is a zoonotic disease that can result in chronic infection in humans. The causative agent, Clonorchis sinensis (C. sinensis), is believed to primarily induce a Th2 immune response in infected mice. However, few studies have profiled host immune responses to C. sinensis infection during the juvenile phase. In the present study, the dynamics of select cellular responses and cytokine expression profiles during juvenile C. sinensis infection were investigated. The flow cytometry results showed that the CD4+ T cells percentage was significantly decreased between 12 days post-infection (dpi) and 24 dpi in the peripheral blood, and the CD8+ T cells percentage was significantly elevated after 3 dpi. The ratio of CD4+/CD8+ T cells was also significantly decreased after 3 dpi. Furthermore, we observed that the proportion of CD14+ monocyte-macrophages in the peripheral blood was significantly increased between 1 dpi and 12 dpi and peaked at 6 dpi. The percentage of classically activated macrophages (M1) and alternatively activated macrophages (M2) in the liver was significantly increased between 18 dpi and 30 dpi. qRT-PCR results showed that the expression levels of iNOS in the liver were significantly elevated after 3 dpi, and Arg-1 expression was significantly increased beginning at 12 dpi. ELISA results showed that the serum levels of the Th1 cytokines IFN-γ and IL-2 peaked at 6 dpi and decreased thereafter. Furthermore, the Th2 cytokines IL-4 and IL-13 began to be expressed and peaked at 24 dpi and 30 dpi, respectively. In addition, the levels of the Treg cytokines IL-10 and TGF-β were significantly increased beginning at 6 dpi until 30 dpi. In the liver homogenate, the expression of IFN-γ, IL-2, and IL-4 mainly occurred before 6 dpi. IL-13 expression was significantly increased at 30 dpi. IL-10 and TGF-β levels were significantly increased at 12 dpi and 24 dpi, and expression peaked at 24 dpi and 30 dpi, respectively. This study provides a fundamental characterization for the future analysis of host-parasite interactions and immune responses in hosts infected with juvenile C. sinensis.

摘要

华支睾吸虫病是一种人畜共患的疾病,可导致人类慢性感染。病原体华支睾吸虫(C.sinensis)被认为主要在感染的小鼠中诱导 Th2 免疫反应。然而,很少有研究描述宿主对幼年华支睾吸虫感染的免疫反应。本研究旨在探讨幼年华支睾吸虫感染过程中特定细胞反应和细胞因子表达谱的动态变化。流式细胞术结果显示,外周血 CD4+T 细胞百分比在感染后 12 天(dpi)和 24 dpi 显著下降,CD8+T 细胞百分比在 3 dpi 后显著升高。3 dpi 后 CD4+/CD8+T 细胞的比值也显著下降。此外,我们观察到外周血中 CD14+单核-巨噬细胞的比例在 1 dpi 和 12 dpi 之间显著增加,并在 6 dpi 时达到峰值。肝内经典激活型巨噬细胞(M1)和选择性激活型巨噬细胞(M2)的比例在 18 dpi 和 30 dpi 之间显著增加。qRT-PCR 结果显示,肝内 iNOS 的表达水平在 3 dpi 后显著升高,Arg-1 的表达从 12 dpi 开始显著增加。ELISA 结果显示,血清中 Th1 细胞因子 IFN-γ和 IL-2 的水平在 6 dpi 时达到峰值,随后下降。此外,Th2 细胞因子 IL-4 和 IL-13 开始表达,并分别在 24 dpi 和 30 dpi 时达到峰值。此外,Treg 细胞因子 IL-10 和 TGF-β的水平在 6 dpi 至 30 dpi 期间显著升高。肝匀浆中 IFN-γ、IL-2 和 IL-4 的表达主要发生在 6 dpi 之前。IL-13 的表达在 30 dpi 时显著增加。IL-10 和 TGF-β的水平在 12 dpi 和 24 dpi 时显著升高,在 24 dpi 和 30 dpi 时达到峰值。本研究为进一步分析宿主感染幼年华支睾吸虫后的宿主-寄生虫相互作用和免疫反应提供了基础。

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