刚地弓形虫 Profilin 和速殖子 RH 株可能通过下调 Atg5 和 Atg12 以及上调 Atg7 来操纵自噬。
Toxoplasma gondii profilin and tachyzoites RH strain may manipulate autophagy via downregulating Atg5 and Atg12 and upregulating Atg7.
机构信息
Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
Mol Biol Rep. 2021 Oct;48(10):7041-7047. doi: 10.1007/s11033-021-06667-5. Epub 2021 Aug 28.
BACKGROUND
Autophagy process is an important defense mechanism against intracellular infection. This process plays a critical role in limiting the development of Toxoplasma gondii. This study aimed to investigate the effects of T. gondii profilin and tachyzoites on the expression of autophagy genes.
METHODS AND RESULTS
PMA-activated THP-1 cell line was incubated with T. gondii profilin and tachyzoites for 6 h. After RNA extraction and cDNA synthesis, the expression of Atg5, Atg7, Atg12, and LC3b was evaluated using real-time PCR. The results revealed statistically significant downregulation of Atg5 for 1.43 (P-value = 0.0062) and 4.15 (P-value = 0.0178) folds after treatment with T. gondii profilin and tachyzoites, respectively. Similar to Atg 5, Atg 12 revealed a statistically significant downregulation for profilin (1.41 fold; P-value = 0.0047) and T. gondii tachyzoites (3.25 fold; P-value = 0.011). The expression of Atg7 elevated in both T. gondii profilin (2.083 fold; P-value = 0.0087) and tachyzoites (1.64 fold; P-value = 0.206). T. gondii profilin and tachyzoites downregulated (1.04 fold; P-value = 0.0028) and upregulated (twofold; P-value = 0.091) the expression of LC3b, respectively.
CONCLUSIONS
Our findings suggest that T. gondii and profilin may manipulate autophagy via preventing from the formation of Atg5-12-16L complex to facilitate replication of T. gondii and development of toxoplasmosis.
背景
自噬过程是一种重要的细胞内感染防御机制。这一过程在限制刚地弓形虫的发展中起着至关重要的作用。本研究旨在探讨刚地弓形虫原肌球蛋白和速殖子对自噬基因表达的影响。
方法和结果
用 PMA 激活的 THP-1 细胞系与刚地弓形虫原肌球蛋白和速殖子孵育 6 小时。提取 RNA 并合成 cDNA 后，用实时 PCR 评估 Atg5、Atg7、Atg12 和 LC3b 的表达。结果显示，在用刚地弓形虫原肌球蛋白和速殖子处理后，Atg5 的表达分别显著下调了 1.43 倍（P 值=0.0062）和 4.15 倍（P 值=0.0178）。与 Atg5 相似，Atg12 的表达也分别显著下调了原肌球蛋白（1.41 倍；P 值=0.0047）和刚地弓形虫速殖子（3.25 倍；P 值=0.011）。T. gondii 原肌球蛋白（2.083 倍；P 值=0.0087）和速殖子（1.64 倍；P 值=0.206）均使 Atg7 的表达升高。刚地弓形虫原肌球蛋白和速殖子分别下调（1.04 倍；P 值=0.0028）和上调（2 倍；P 值=0.091）LC3b 的表达。
结论
我们的研究结果表明，刚地弓形虫和原肌球蛋白可能通过阻止 Atg5-12-16L 复合物的形成来操纵自噬，从而促进刚地弓形虫的复制和弓形虫病的发展。
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