Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers
Post-print (lokagerð höfundar) 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...
Published in: | Infection and Immunity |
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Language: | English |
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American Society for Microbiology
2017
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Online Access: | https://hdl.handle.net/20.500.11815/2008 https://doi.org/10.1128/IAI.00445-17 |
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ftopinvisindi:oai:opinvisindi.is:20.500.11815/2008 2023-05-15T16:52:07+02:00 Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers Hasan, Shakir Kulkarni, Nikhil Nitin Asbjarnarson, Arni Linhartova, Irena Osicka, Radim Sebo, Peter Gudmundsson, Gudmundur H Lífvísindasetur (HÍ) Biomedical Center (UI) Verkfræði- og náttúruvísindasvið (HÍ) School of Engineering and Natural Sciences (UI) Háskóli Íslands University of Iceland 2017-12-04 e00445-17 https://hdl.handle.net/20.500.11815/2008 https://doi.org/10.1128/IAI.00445-17 en eng American Society for Microbiology Infection and Immunity;86(3) https://syndication.highwire.org/content/doi/10.1128/IAI.00445-17 Hasan S, Kulkarni NN, Asbjarnarson A, Linhartova I, Osicka R, Sebo P, Gudmundsson GH. 2018. Bordetella pertussis adenylate cyclase toxin disrupts functional integrity of bronchial epithelial layers. Infect Immun 86:e00445-17. https://doi.org/10.1128/IAI.00445-17 0019-9567 1098-5522 (eISSN) https://hdl.handle.net/20.500.11815/2008 Infection and Immunity doi:10.1128/IAI.00445-17 info:eu-repo/semantics/openAccess Bordetella pertussis Airway epithelia Antimicrobial peptides Lungnasjúkdómar Öndunarfærasjúkdómar Peptíð Ónæmisfræði info:eu-repo/semantics/article 2017 ftopinvisindi https://doi.org/20.500.11815/2008 https://doi.org/10.1128/IAI.00445-17 2022-11-18T06:51:59Z Post-print (lokagerð höfundar) 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. We are grateful to Branislav Vecerek for providing anti-Bordetella serum. Christine Terryn graciously provided the macro for evaluating TiJOR. Blanka Jurkova is acknowledged for excellent technical help. This work was supported by a grant to Gudmundur H. Gudmundsson from the Icelandic Centre for Research (RANNIS - 152370) and the University of Iceland Research Fund. Further support came from Czech CSF grants GA15-09157S (to R.O.), GA18-20621S (to P.S.), and NV16-28126A (to P.S.); grant LM2015064 from the Ministry of Education, Youth and Sports ... Article in Journal/Newspaper Iceland Opin vísindi (Iceland) Infection and Immunity 86 3 |
institution |
Open Polar |
collection |
Opin vísindi (Iceland) |
op_collection_id |
ftopinvisindi |
language |
English |
topic |
Bordetella pertussis Airway epithelia Antimicrobial peptides Lungnasjúkdómar Öndunarfærasjúkdómar Peptíð Ónæmisfræði |
spellingShingle |
Bordetella pertussis Airway epithelia Antimicrobial peptides Lungnasjúkdómar Öndunarfærasjúkdómar Peptíð Ónæmisfræði Hasan, Shakir Kulkarni, Nikhil Nitin Asbjarnarson, Arni Linhartova, Irena Osicka, Radim Sebo, Peter Gudmundsson, Gudmundur H Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers |
topic_facet |
Bordetella pertussis Airway epithelia Antimicrobial peptides Lungnasjúkdómar Öndunarfærasjúkdómar Peptíð Ónæmisfræði |
description |
Post-print (lokagerð höfundar) 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. We are grateful to Branislav Vecerek for providing anti-Bordetella serum. Christine Terryn graciously provided the macro for evaluating TiJOR. Blanka Jurkova is acknowledged for excellent technical help. This work was supported by a grant to Gudmundur H. Gudmundsson from the Icelandic Centre for Research (RANNIS - 152370) and the University of Iceland Research Fund. Further support came from Czech CSF grants GA15-09157S (to R.O.), GA18-20621S (to P.S.), and NV16-28126A (to P.S.); grant LM2015064 from the Ministry of Education, Youth and Sports ... |
author2 |
Lífvísindasetur (HÍ) Biomedical Center (UI) Verkfræði- og náttúruvísindasvið (HÍ) School of Engineering and Natural Sciences (UI) Háskóli Íslands University of Iceland |
format |
Article in Journal/Newspaper |
author |
Hasan, Shakir Kulkarni, Nikhil Nitin Asbjarnarson, Arni Linhartova, Irena Osicka, Radim Sebo, Peter Gudmundsson, Gudmundur H |
author_facet |
Hasan, Shakir Kulkarni, Nikhil Nitin Asbjarnarson, Arni Linhartova, Irena Osicka, Radim Sebo, Peter Gudmundsson, Gudmundur H |
author_sort |
Hasan, Shakir |
title |
Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers |
title_short |
Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers |
title_full |
Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers |
title_fullStr |
Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers |
title_full_unstemmed |
Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers |
title_sort |
bordetella pertussis adenylate cyclase toxin disrupts functional integrity of bronchial epithelial layers |
publisher |
American Society for Microbiology |
publishDate |
2017 |
url |
https://hdl.handle.net/20.500.11815/2008 https://doi.org/10.1128/IAI.00445-17 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
Infection and Immunity;86(3) https://syndication.highwire.org/content/doi/10.1128/IAI.00445-17 Hasan S, Kulkarni NN, Asbjarnarson A, Linhartova I, Osicka R, Sebo P, Gudmundsson GH. 2018. Bordetella pertussis adenylate cyclase toxin disrupts functional integrity of bronchial epithelial layers. Infect Immun 86:e00445-17. https://doi.org/10.1128/IAI.00445-17 0019-9567 1098-5522 (eISSN) https://hdl.handle.net/20.500.11815/2008 Infection and Immunity doi:10.1128/IAI.00445-17 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/20.500.11815/2008 https://doi.org/10.1128/IAI.00445-17 |
container_title |
Infection and Immunity |
container_volume |
86 |
container_issue |
3 |
_version_ |
1766042259346685952 |