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弓形虫 ROP18 抑制 C17.2 神经干细胞分化的机制研究。

A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of C17.2 neural stem cells.

机构信息

Department of Microbiology and Parasitology; Anhui Provincial Laboratory of Microbiology and Parasitology; Anhui Key Laboratory of Zoonoses, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People's Republic of China.

Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei, 230039, People's Republic of China.

出版信息

Parasit Vectors. 2017 Nov 23;10(1):585. doi: 10.1186/s13071-017-2529-2.

DOI:10.1186/s13071-017-2529-2
PMID:29169404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5701453/
Abstract

BACKGROUND

Congenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs) are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive.

RESULTS

In the present study, ROP18 recombinant adenovirus (Ad-ROP18) was constructed and used to infect C17.2 NSCs. After 3d- or 5d-culture in differentiation medium, the differentiation of C17.2 NSCs and the activity of the Wnt/β-catenin signaling pathway were detected. The results showed that the protein level of βIII-tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was significantly decreased, indicating that the differentiation of C17.2 NSCs was inhibited by the ROP18. The β-catenin level in the Ad-ROP18-transfected C17.2 NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1) and neurogenin2 (Ngn2) were downregulated significantly (P < 0.05) in the Ad-ROP18-transfected C17.2 NSCs compared to the Ad group. Accordingly, the TOP flash/FOP flash dual-luciferase report system showed that the transfection of Ad-ROP18 decreased the Wnt/β-catenin pathway activity in the C17.2 NSCs.

CONCLUSIONS

The inhibition effect of the ROP18 from T. gondii (TgROP18) on the neuronal differentiation of C17.2 NSCs was at least partly mediated through inhibiting the activity of the Wnt/β-catenin signaling pathway, eventually resulting in the downregulation of Ngn1 and Ngn2. The findings help to better understand potential mechanisms of brain pathology induced by TgROP18.

摘要

背景

弓形虫先天性感染是导致出生缺陷的一个重要因素。神经干细胞（NSCs）被发现是寄生虫在大脑发育过程中的靶细胞之一。ROP18 作为寄生虫的关键毒力因子，已被证明通过与不同的宿主免疫相关分子特异性结合来介导对宿主固有和适应性免疫反应的抑制。然而，其在 NSCs 中的致病作用仍不清楚。

结果

本研究构建了 ROP18 重组腺病毒（Ad-ROP18）并用于感染 C17.2 NSCs。在分化培养基中培养 3d 或 5d 后，检测 C17.2 NSCs 的分化和 Wnt/β-catenin 信号通路的活性。结果表明，Ad-ROP18 转染的 C17.2 NSCs 中神经元标志物 βIII-微管蛋白的蛋白水平明显降低，表明 ROP18 抑制了 C17.2 NSCs 的分化。Ad-ROP18 转染的 C17.2 NSCs 中的β-catenin 水平低于 Ad 组。此外，与 Ad 组相比，Ad-ROP18 转染的 C17.2 NSCs 中神经基因 1（Ngn1）和神经基因 2（Ngn2）显著下调（P<0.05）。相应地，TOP flash/FOP flash 双荧光素酶报告系统显示，Ad-ROP18 的转染降低了 C17.2 NSCs 中 Wnt/β-catenin 通路的活性。

结论

弓形虫 TgROP18 的 ROP18 对 C17.2 NSCs 神经元分化的抑制作用至少部分是通过抑制 Wnt/β-catenin 信号通路的活性来介导的，最终导致 Ngn1 和 Ngn2 的下调。这些发现有助于更好地了解 TgROP18 引起的脑病理学的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/f4df83a654d9/13071_2017_2529_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/b42cb2363e3c/13071_2017_2529_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/66d2f69463ce/13071_2017_2529_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/3f22109929cd/13071_2017_2529_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/1065f22d14ad/13071_2017_2529_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/6543a9606e71/13071_2017_2529_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/f4df83a654d9/13071_2017_2529_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/b42cb2363e3c/13071_2017_2529_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/66d2f69463ce/13071_2017_2529_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/3f22109929cd/13071_2017_2529_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/1065f22d14ad/13071_2017_2529_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/6543a9606e71/13071_2017_2529_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9233/5701453/f4df83a654d9/13071_2017_2529_Fig6_HTML.jpg

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2
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4
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5
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6
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8
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9
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10
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