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PNAS:中大生科院发表弓形虫研究重要成果

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摘要 : 中山大学和加州大学的研究团队发现,弓形虫感染会抑制呼吸道的氯离子分泌,影响其清除病原体的能力。这一成果发表在三月二十三日的美国国家科学院院刊PNAS杂志上。

PNAS:中大生科院发表弓形虫研究重要成果

弓形虫(Toxoplasma gondii)是一种寄生在细胞内的病原体,可以感染包括人在内的几乎所有的温血动物。弓形虫感染引起的肺部疾病,对新生儿、儿童和存在免疫力低下人(AIDS、骨髓移植、器官移植等)特别危险。

呼吸道上皮细胞能够调节机体对多种病原体的免疫应答。不过,目前人们还不清楚弓形虫感染对呼吸道上皮细胞的具体影响。

中山大学和加州大学的研究团队发现,弓形虫感染会抑制呼吸道的氯离子分泌,影响其清除病原体的能力。这一成果发表在三月二十三日的美国国家科学院院刊PNAS杂志上,文章的通讯作者是中山大学生命科学院的伦照荣(Zhao-Rong Lun)教授、周文良(Wen-Liang Zhou)教授和加州大学的Francisco J. Ayala。

呼吸道的黏液纤毛系统能够清除吸入性的病原体,而CFTR(囊性纤维化跨膜传导因子)介导的氯离子分泌在这一过程中起到了重要的作用。研究人员使用短路电流技术(Isc),在弓形虫感染的气管上皮细胞中分析了atp诱导的氯离子分泌。研究显示,弓形虫感染会显著抑制这种ATP诱导的氯离子分泌。

研究人员还通过实时定量pcr发现,在弓形虫感染的小鼠气管中,P2Y2受体的mRNA表达水平显著增加。这说明,弓形虫感染呼吸道的潜在机制与P2Y2受体有关。

研究指出,弓形虫感染会通过P2Y2-R影响宿主细胞的氯离子分泌。这一发现有助于人们进一步理解弓形虫感染对宿主产生的影响,并在此基础上开发相应的治疗策略。

原文链接:Infection by Toxoplasma gondii, a severe parasite in neonates and AIDS patients, causes impaired anion secretion in airway epithelia

The airway epithelia initiate and modulate the inflammatory responses to various pathogens. The cystic fibrosis transmembrane conductance regulator-mediated Cl− secretion system plays a key role in mucociliary clearance of inhaled pathogens. We have explored the effects of Toxoplasma gondii, an opportunistic intracellular protozoan parasite, on Cl− secretion of the mouse tracheal epithelia. In this study, ATP-induced Cl− secretion indicated the presence of a biphasic short-circuit current (Isc) response, which was mediated by a Ca2+-activated Cl− channel (CaCC) and the cystic fibrosis transmembrane conductance regulator. However, the ATP-evoked Cl− secretion in T. gondii-infected mouse tracheal epithelia and the elevation of [Ca2+]i in T. gondii-infected human airway epithelial cells were suppressed. Quantitative reverse transcription–PCR revealed that the mRNA expression level of the P2Y2 receptor (P2Y2-R) increased significantly in T. gondii-infected mouse tracheal cells. This revealed the influence that pathological changes in P2Y2-R had on the downstream signal, suggesting that P2Y2-R was involved in the mechanism underlying T. gondii infection in airways. These results link T. gondii infection as well as other pathogen infections to Cl− secretion, via P2Y2-R, which may provide new insights for the treatment of pneumonia caused by pathogens including T. gondii.

作者:Hong-Mei Guo 点击:

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