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.

• 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
• Electronic ISSN: 1091-6490
• 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