PNAS 2015-04-07

Infection by Toxoplasma gondii, a severe parasite in neonates and AIDS patients, causes impaired anion secretion in airway epithelia.

Hong-Mei Guo, Jiang-Mei Gao, Yu-Li Luo, Yan-Zi Wen, Yi-Lin Zhang, Geoff Hide, Wen-Liang Zhou, Francisco J Ayala, Zhao-Rong Lun

文献索引：Proc. Natl. Acad. Sci. U. S. A. 112(14) , 4435-40, (2015)

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摘要

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 Ca(2+)-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 [Ca(2+)]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.