1. Academic Validation
  2. Toxoplasma gondii infection triggers ongoing inflammation mediated by increased intracellular Cl- concentration in airway epithelium

Toxoplasma gondii infection triggers ongoing inflammation mediated by increased intracellular Cl- concentration in airway epithelium

  • J Infect. 2022 Nov 2;S0163-4453(22)00635-1. doi: 10.1016/j.jinf.2022.10.037.
Zhuo-Er Qiu 1 Lei Chen 1 Xiao-Chun Hou 1 Jie Sheng 1 Jian-Bang Xu 2 Jia-Wen Xu 1 Dong-Dong Gao 3 Ze-Xin Huang 1 Tian-Lun Lei 1 Zi-Yang Huang 1 Lei Peng 1 Hai-Long Yang 1 Qin-Hua Lin 1 Yun-Xin Zhu 1 Wei-Jie Guan 4 Zhao-Rong Lun 1 Wen-Liang Zhou 5 Yi-Lin Zhang 6
Affiliations

Affiliations

  • 1 School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • 2 School of Life Sciences, Sun Yat-sen University, Guangzhou, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
  • 3 School of Life Sciences, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Scientific Research Center, Guangzhou Sport University, Guangzhou, China.
  • 4 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
  • 5 School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: [email protected]
  • 6 School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: [email protected]
Abstract

Toxoplasma gondii is a widespread parasitic protozoan causing pulmonary toxoplasmosis. As the first line of host defense, airway epithelial cells play critical roles in orchestrating pulmonary innate immunity. However, the mechanism underlying the airway inflammation induced by the T. gondii Infection remains largely unclear. This study demonstrated that after Infection with T. gondii, the major anion channel located in the apical membranes of airway epithelial cells, cystic fibrosis transmembrane conductance regulator (CFTR), was degraded by the parasite-secreted cysteine proteases. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to activation of nuclear factor-κB (NF-κB) signaling via serum/glucocorticoid regulated kinase 1. Furthermore, the heightened [Cl-]i and activated NF-κB signaling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP level through NF-κB-mediated up-regulation of phosphodiesterase 4. Conversely, the sulfur-containing compound allicin conferred anti-inflammatory effects on pulmonary toxoplasmosis by decreasing [Cl-]i via activation of CFTR. These results suggest that the intracellular Cl- dynamically modulated by T. gondii mediates sustained airway inflammation, which provides a potential therapeutic target against pulmonary toxoplasmosis.

Keywords

Airway inflammation; Allicin; CFTR; Toxoplasma gondii; intracellular Cl(−) signaling.

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