Zhi-Cheng Liu1, Min Wang2, Wen-Kui Sun2, Di Xia2, Ming-Ming Tan2, Yuan Ding2, Qian Qian3, Xin Su2, Yi Shi2. 1. Southern Medical University Guangdong, People's Republic of China. 2. Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University Nanjing, People's Republic of China. 3. Nanjing Chest Hospital Nanjing, People's Republic of China.
Abstract
INTRODUCTION: With the growing number of immunocompromised patients, the incidence of invasive pulmonary aspergillosis increases. Innate immunity plays a significant role in defensing against fungal infection. Airway epithelial cells induce immune responses like the production of cytokine and chemokine via Dectin-1 signaling pathway in response to Aspergillus fumigatus. Thus, we hypothesized that up-regulation of Dectin-1 on airway epithelium cells would promote the defense against A. fumigatus. METHODS: We designed an adenoviral vector encoding full-length Dectin-1, and then transfected it into mice airway epithelial cells via intratracheal injection before the invasion of A. fumigatus. Transfect mice model was verified by using real-time PCR and immunohistochemistry. And also, we studied the effects of up-regulation of Dectin-1 on the production of proinflammatory cytokines, histological changes, fungal burden and survival rate during A. fumigatus infection. RESULTS: The expression level of Dectin-1 in lungs of mice with Dectin-1 recombinant adenoviral vector significantly increased. And also, the mice had higher production of TNF-α, GM-CSF and IL-1β, lower fungal burden, more recruitment of neutrophils into lungs and higher survival rate in response to A. fumigatus infection. CONCLUSIONS: The administration of Dectin-1 recombinant adenoviral vector through trachea can elevate the expression of Dectin-1 on airway epithelium, and also, its function during the course of A. fumigatus infection was demonstrated.
INTRODUCTION: With the growing number of immunocompromised patients, the incidence of invasive pulmonary aspergillosis increases. Innate immunity plays a significant role in defensing against fungal infection. Airway epithelial cells induce immune responses like the production of cytokine and chemokine via Dectin-1 signaling pathway in response to Aspergillus fumigatus. Thus, we hypothesized that up-regulation of Dectin-1 on airway epithelium cells would promote the defense against A. fumigatus. METHODS: We designed an adenoviral vector encoding full-length Dectin-1, and then transfected it into mice airway epithelial cells via intratracheal injection before the invasion of A. fumigatus. Transfect mice model was verified by using real-time PCR and immunohistochemistry. And also, we studied the effects of up-regulation of Dectin-1 on the production of proinflammatory cytokines, histological changes, fungal burden and survival rate during A. fumigatusinfection. RESULTS: The expression level of Dectin-1 in lungs of mice with Dectin-1 recombinant adenoviral vector significantly increased. And also, the mice had higher production of TNF-α, GM-CSF and IL-1β, lower fungal burden, more recruitment of neutrophils into lungs and higher survival rate in response to A. fumigatusinfection. CONCLUSIONS: The administration of Dectin-1 recombinant adenoviral vector through trachea can elevate the expression of Dectin-1 on airway epithelium, and also, its function during the course of A. fumigatusinfection was demonstrated.
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