Molecular characterization of pulmonary defenses against bacterial invasion in allergic asthma: The role of Foxa2 in regulation of β-defensin 1

Autoři: Chuanqi Wei aff001;  Xiaoju Tang aff001;  Faping Wang aff001;  Yan Li aff001;  Lin Sun aff001;  Fengming Luo aff001
Působiště autorů: Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Guo Xue Xiang, Chengdu, China aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Allergic asthma, characterized by chronic airway Th2-dominated inflammation, is associated with an increased risk of infection; however, the underlying mechanisms are unclear. Forkhead box protein A2 (Foxa2) plays a critical role in Th2 inflammation and is associated with pulmonary defenses. To determining the role of Foxa2 in Th2-dominated lung inflammation against the invading bacteria, we established a mouse OVA-sensitized model, an Escherichia coli lung invasion model, and mice with conditional deletion of Foxa2 in respiratory epithelial cells. The number of bacteria in the lung tissue was counted to assess clearance ability of lung. Lung inflammation and histopathology was evaluated using HE and PAS staining. It was found that OVA-sensitized mice had decreased E. coli clearance, reduced Foxa2 expression, and decreased DEFB1 secretion. Conditional deletion of Foxa2 in respiratory epithelial cells led to decreased clearance of E. coli and impaired secretion of DEFB1, similar to the OVA-induced allergic condition. The impaired secretion of DEFB1 may be responsible for the increased risk of infection in the Th2-dominated airway inflammation. Dual luciferase assay demonstrated that Foxa2 regulates DEFB1 expression by affecting its promoter activity in HBE cells. Our study indicated that Foxa2 plays an important role in Th2-dominated airway inflammation against invading bacteria. Conditional deletion of Foxa2 in respiratory epithelial cells can reduce pulmonary’s defense against bacterial invasion by inhibiting DEFB1expression.

Klíčová slova:

Asthma – Enzyme-linked immunoassays – Epithelial cells – Gene expression – Inflammation – Luciferase – Secretion – Transfection


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2019 Číslo 12
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