弓形蟲(Toxoplasma gondii)是一種寄生在細胞內(nèi)的病原體，可以感染包括人在內(nèi)的幾乎所有的溫血動物。弓形蟲感染引起的肺部疾病，對新生兒、兒童和存在免疫力低下人(AIDS、骨髓移植、器官移植等)特別危險。

呼吸道上皮細胞能夠調(diào)節(jié)機體對多種病原體的免疫應(yīng)答。不過，目前人們還不清楚弓形蟲感染對呼吸道上皮細胞的具體影響。

中山大學(xué)和加州大學(xué)的研究團隊發(fā)現(xiàn)，弓形蟲感染會抑制呼吸道的氯離子分泌，影響其清除病原體的能力。這一成果發(fā)表在三月二十三日的美國國家科學(xué)院院刊PNAS雜志上，文章的通訊作者是中山大學(xué)生命科學(xué)院的倫照榮(Zhao-Rong Lun)教授、周文良(Wen-Liang Zhou)教授和加州大學(xué)的Francisco J. Ayala。

呼吸道的黏液纖毛系統(tǒng)能夠清除吸入性的病原體，而CFTR(囊性纖維化跨膜傳導(dǎo)因子)介導(dǎo)的氯離子分泌在這一過程中起到了重要的作用。研究人員使用短路電流技術(shù)(Isc)，在弓形蟲感染的氣管上皮細胞中分析了atp誘導(dǎo)的氯離子分泌。研究顯示，弓形蟲感染會顯著抑制這種ATP誘導(dǎo)的氯離子分泌。

研究人員還通過實時定量pcr發(fā)現(xiàn)，在弓形蟲感染的小鼠氣管中，P2Y2受體的mRNA表達水平顯著增加。這說明，弓形蟲感染呼吸道的潛在機制與P2Y2受體有關(guān)。

研究指出，弓形蟲感染會通過P2Y2-R影響宿主細胞的氯離子分泌。這一發(fā)現(xiàn)有助于人們進一步理解弓形蟲感染對宿主產(chǎn)生的影響，并在此基礎(chǔ)上開發(fā)相應(yīng)的治療策略。

原文鏈接：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.