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

Guo, H-M; Gao, J-M; Luo, Y-L; Wen, Y-Z; Zhang, Y-L; Hide, G; Zhou, W-L; Ayala, FJ; Lun, Z-R

Abstract

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.

Citation

Guo, H., Gao, J., Luo, Y., Wen, Y., Zhang, Y., Hide, G., …Lun, Z. (2015). Infection by Toxoplasma gondii, a severe parasite in neonates and AIDS patients, causes impaired anion secretion in airway epithelia. Proceedings of the National Academy of Sciences, 112(14), 4435-40. https://doi.org/10.1073/pnas.1503474112

• Journal Article Type: Article
• Acceptance Date: Feb 20, 2015
• Online Publication Date: Mar 23, 2015
• Publication Date: Apr 7, 2015
• Deposit Date: May 8, 2015
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 112
• Issue: 14
• Pages: 4435-40
• DOI: https://doi.org/10.1073/pnas.1503474112
• Publisher URL: http://dx.doi.org/10.1073/pnas.1503474112
• Related Public URLs: http://www.pnas.org/
• Additional Information: Funders : National Science Foundation of China;National Basic Research Programme of China; Grant Number: 30770817; Grant Number: 2009CB522102; Grant Number: 2010CB530000; Grant Number: 973 Programme