Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin

Frontiers in Cellular and Infection Microbiology

Heike Oberwinkler¹  Niklas Pallmann¹  Rinu Sivarajan¹  Maria Steinke²  David Komla Kessie³  Stephan Hackenberg⁴  Agmal Scherzad⁵  Thorsten Walles⁶ 

[1] Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany;Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany;Translational Center Regenerative Therapies, Fraunhofer Institute for Silicate Research ISC, Würzburg, Germany;Department of Microbiology, University of Würzburg, Würzburg, Germany;Department of Oto-Rhino-Laryngology – Head and Neck Surgery, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) Aachen University Hospital, Aachen, Germany;Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, Würzburg, Germany;Department of Thoracic Surgery, University Medicine Magdeburg, Magdeburg, Germany;

关键词: human nasal epithelial cells;    human tracheo-bronchial epithelial cells;    human airway mucosa tissue models;    adenylate cyclase toxin;    Bordetella pertussis;   

DOI  :  10.3389/fcimb.2021.797491

来源: Frontiers

【 摘 要 】

To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC-. Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens.

【 授权许可】

CC BY