@article{SivarajanKessieOberwinkleretal.2021,
  author    = {Sivarajan, Rinu and Kessie, David Komla and Oberwinkler, Heike and Pallmann, Niklas and Walles, Thorsten and Scherzad, Agmal and Hackenberg, Stephan and Steinke, Maria},
  title     = {Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {11},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2021.797491},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-253302},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{BianchiSivarajanWallesetal.2021,
  author    = {Bianchi, Maria and Sivarajan, Rinu and Walles, Thorsten and Hackenberg, Stephan and Steinke, Maria},
  title     = {Susceptibility of primary human airway epithelial cells to Bordetella pertussis adenylate cyclase toxin in two- and three-dimensional culture conditions},
  series = {Innate Immunity},
  volume    = {27},
  journal   = {Innate Immunity},
  number    = {1},
  issn      = {1753-4259},
  doi       = {10.1177/1753425920979354},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219849},
  pages     = {89-98},
  year      = {2021},
  abstract  = {The human pathogen Bordetella pertussis targets the respiratory epithelium and causes whooping cough. Its virulence factor adenylate cyclase toxin (CyaA) plays an important role in the course of infection. Previous studies on the impact of CyaA on human epithelial cells have been carried out using cell lines derived from the airways or the intestinal tract. Here, we investigated the interaction of CyaA and its enzymatically inactive but fully pore-forming toxoid CyaA-AC- with primary human airway epithelial cells (hAEC) derived from different anatomical sites (nose and tracheo-bronchial region) in two-dimensional culture conditions. To assess possible differences between the response of primary hAEC and respiratory cell lines directly, we included HBEC3-KT in our studies. In comparative analyses, we studied the impact of both the toxin and the toxoid on cell viability, intracellular cAMP concentration and IL-6 secretion. We found that the selected hAEC, which lack CD11b, were differentially susceptible to both CyaA and CyaA-AC-. HBEC3-KT appeared not to be suitable for subsequent analyses. Since the nasal epithelium first gets in contact with airborne pathogens, we further studied the effect of CyaA and its toxoid on the innate immunity of three-dimensional tissue models of the human nasal mucosa. The present study reveals first insights in toxin-cell interaction using primary hAEC.},
  language  = {en}
}