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Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers
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SYSNO ASEP 0488787 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers Author(s) Hasan, Shakir (MBU-M)
Kulkarni, N.N. (IS)
Asbjarnarson, A. (IS)
Linhartová, Irena (MBU-M) RID, ORCID
Osička, Radim (MBU-M) RID, ORCID
Šebo, Peter (MBU-M) RID, ORCID
Gudmundsson, H. (IS)Article number e00445-17 Source Title Infection and Immunity. - : American Society for Microbiology - ISSN 0019-9567
Roč. 86, č. 3 (2018)Number of pages 19 s. Language eng - English Country US - United States Keywords Bordetella pertussis ; airway epithelia ; CyaA Subject RIV EE - Microbiology, Virology OECD category Microbiology R&D Projects GA15-09157S GA ČR - Czech Science Foundation (CSF) NV16-28126A GA MZd - Ministry of Health (MZ) LM2015064 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA18-20621S GA ČR - Czech Science Foundation (CSF) EF16_013/0001818 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support MBU-M - RVO:61388971 UT WOS 000425510700008 EID SCOPUS 85042315699 DOI 10.1128/IAI.00445-17 Annotation The airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent, Bordetella pertussis, adheres to ciliated cells of the human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We examined the impact of B. pertussis infection and of adenylate cyclase toxin-hemolysin (CyaA) action on the functional integrity of human bronchial epithelial cells cultured at the air-liquid interface (ALI). B. pertussis adhesion to the apical surface of polarized pseudostratified VA10 cell layers provoked a disruption of tight junctions and caused a drop in transepithelial electrical resistance (TEER). The reduction of TEER depended on the capacity of the secreted CyaA toxin to elicit cAMP signaling in epithelial cells through its adenylyl cyclase enzyme activity. Both purified CyaA and cAMP-signaling drugs triggered a decrease in the TEER of VA10 cell layers. Toxin-produced cAMP signaling caused actin cytoskeleton rearrangement and induced mucin 5AC production and interleukin-6 (IL-6) secretion, while it inhibited the IL-17A-induced secretion of the IL-8 chemokine and of the antimicrobial peptide beta-defensin 2. These results indicate that CyaA toxin activity compromises the barrier and innate immune functions of Bordetella-infected airway epithelia. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2019
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