{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:19:00Z","timestamp":1793035140598,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>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 <jats:italic>Bordetella pertussis<\/jats:italic> 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 <jats:italic>B. pertussis<\/jats:italic> virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC<jats:sup>-<\/jats:sup>. Applying molecular biological, histological, and microbiological assays, we found that 1 \u00b5g\/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 <jats:italic>B. pertussis<\/jats:italic> 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 <jats:italic>B. pertussis<\/jats:italic> CyaA <jats:italic>in vitro<\/jats:italic>. Our finding that nasal tissue models showed an increased innate immune response towards the <jats:italic>B. pertussis<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fcimb.2021.797491","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:14:44Z","timestamp":1640254484000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin"],"prefix":"10.3389","volume":"11","author":[{"given":"Rinu","family":"Sivarajan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Komla","family":"Kessie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Oberwinkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Pallmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Walles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agmal","family":"Scherzad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Hackenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Steinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1111\/resp.12692","article-title":"Comparison of Innate Immune Responses Towards Rhinovirus Infection of Primary Nasal and Bronchial Epithelial Cells","volume":"21","author":"Alves","year":"2016","journal-title":"Respirology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0228606","DOI":"10.1371\/journal.pone.0228606","article-title":"Functional and Structural Consequences of Epithelial Cell Invasion by Bordetella Pertussis Adenylate Cyclase Toxin","volume":"15","author":"Angely","year":"2020","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5530","DOI":"10.1128\/IAI.72.9.5530-5533.2004","article-title":"Bordetella Pertussis Adenylate Cyclase-Hemolysin Induces Interleukin-6 Secretion by Human Tracheal Epithelial Cells","volume":"72","author":"Bassinet","year":"2004","journal-title":"Infect. 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