title: Infection by Toxoplasma gondii, a severe parasite in neonates and AIDS patients, causes impaired anion secretion in airway epithelia.
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.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China; Biology and Food Engineering Institute, Guangdong University of Education, Guangzhou 510303, P.R. China;
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China; Key Laboratory for Tropical Diseases Control of the Ministry of Education, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou 510080, P.R. China;
authors.forename: Jiang-Mei
authors.initials: JM
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China;
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China; Key Laboratory for Tropical Diseases Control of the Ministry of Education, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou 510080, P.R. China;
authors.forename: Yan-Zi
authors.initials: YZ
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China;
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Greater Manchester, Salford M5 4WT, United Kingdom;
authors.forename: Geoff
authors.initials: G
authors.lastname: Hide
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China; lsszwl@mail.sysu.edu.cn fjayala@uci.edu lsslzr@mail.sysu.edu.cn.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Zhou
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697; and lsszwl@mail.sysu.edu.cn fjayala@uci.edu lsslzr@mail.sysu.edu.cn.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ayala
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, P.R. China; Key Laboratory for Tropical Diseases Control of the Ministry of Education, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou 510080, P.R. China; Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Greater Manchester, Salford M5 4WT, United Kingdom; Shenzhen Research and Development Center of State Key Laboratory of Biocontrol, Sun Yat-Sen University, Baoan, Shenzhen 518057, P.R. China lsszwl@mail.sysu.edu.cn fjayala@uci.edu lsslzr@mail.sysu.edu.cn.
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000469:parasitology*; D006801:Humans; D017136:Ion Transport; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism; D015398:Signal Transduction; D014122:Toxoplasma / Q000472:pathogenicity*; D014132:Trachea / Q000469:parasitology
chemical_list: D000838:Anions; C505032:CFTR protein, human; D002712:Chlorides; D012333:RNA, Messenger; D058473:Receptors, Purinergic P2Y2; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ATP; Cl− secretion; P2Y2 receptor; cystic fibrosis; pneumonia
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