TY  - JOUR
A1  - Kessie, David K.
A1  - Lodes, Nina
A1  - Oberwinkler, Heike
A1  - Goldman, William E.
A1  - Walles, Thorsten
A1  - Steinke, Maria
A1  - Gross, Roy
T1  - Activity of Tracheal Cytotoxin of Bordetella pertussis in a Human Tracheobronchial 3D Tissue Model
T2  - Frontiers in Cellular and Infection Microbiology
N2  - Bordetella pertussis is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by B. pertussis that has been able to recapitulate this pathology in animal models. This pathophysiology is well characterized in a hamster tracheal model, but human data are lacking due to scarcity of donor material. We assessed the impact of TCT and lipopolysaccharide (LPS) on the functional integrity of the human airway mucosa by using in vitro airway mucosa models developed by co-culturing human tracheobronchial epithelial cells and human tracheobronchial fibroblasts on porcine small intestinal submucosa scaffold under airlift conditions. TCT and LPS either alone and in combination induced blebbing and necrosis of the ciliated epithelia. TCT and LPS induced loss of ciliated epithelial cells and hyper-mucus production which interfered with mucociliary clearance. In addition, the toxins had a disruptive effect on the tight junction organization, significantly reduced transepithelial electrical resistance and increased FITC-Dextran permeability after toxin incubation. In summary, the results indicate that TCT collaborates with LPS to induce the disruption of the human airway mucosa as reported for the hamster tracheal model.
KW  - tracheal cytotoxin
KW  - airway epithelia
KW  - tissue model
KW  - ciliostasis
KW  - tight junction
KW  - Bordetella pertussis
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/22273
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-222736
SN  - 2235-2988
VL  - 10
ER  -