Modulation of human airway barrier functions during Burkholderia thailandensis and Francisella tularensis Infection: Running Title: Airway Barrier Functions during Bacterial Infections
Modulation of human airway barrier functions during Burkholderia thailandensis and Francisella tularensis Infection: Running Title: Airway Barrier Functions during Bacterial Infections
The bronchial epithelium provides protection against pathogens from the inhaled environment through the formation of a highly-regulated barrier. In order to understand the pulmonary diseases melioidosis and tularemia caused by Burkholderia thailandensis and Fransicella tularensis, respectively, the barrier function of the human bronchial epithelium were analysed. Polarised 16HBE14o- or differentiated primary human bronchial epithelial cells (BECs) were exposed to increasing multiplicities of infection (MOI) of B. thailandensis or F. tularensis Live Vaccine Strain and barrier responses monitored over 24–72 h. Challenge of polarized BECs with either bacterial species
caused an MOI- and time-dependent increase in ionic permeability, disruption of tight junctions, and bacterial passage from the apical to the basolateral compartment. B. thailandensis was found to be more invasive than F. tularensis. Both bacterial species induced an MOI-dependent increase in TNF-α release. An increase in ionic permeability and TNF-α release was induced by B. thailandensis in differentiated BECs. Pretreatment of polarised BECs with the corticosteroid fluticasone propionate reduced bacterial-dependent increases in ionic permeability, bacterial passage, and TNF-α release.
TNF blocking antibody Enbrel® reduced bacterial passage only. BEC barrier properties are disrupted during respiratory bacterial infections and targeting with corticosteroids or anti-TNF compounds may represent a therapeutic option.
Journal Article
1-14
Blume, Cornelia
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David, Jonathan
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Bell, Rachel E.
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Laver, Jay R.
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Read, Robert C.
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Clark, Graeme C.
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Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
3 August 2016
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
David, Jonathan
28818259-8a39-4411-8cb6-cfc199418d38
Bell, Rachel E.
e9c3f774-29f2-4623-9719-a1f083016ac8
Laver, Jay R.
b2996398-2ccf-40f0-92b8-f338f3de796b
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Clark, Graeme C.
5ec11c99-53e2-47aa-82b1-2cd18c6c0449
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Blume, Cornelia, David, Jonathan, Bell, Rachel E., Laver, Jay R., Read, Robert C., Clark, Graeme C., Davies, Donna E. and Swindle, Emily J.
(2016)
Modulation of human airway barrier functions during Burkholderia thailandensis and Francisella tularensis Infection: Running Title: Airway Barrier Functions during Bacterial Infections.
[in special issue: Host Defense Against Bacteria]
Pathogens, 5 (3), , [53].
(doi:10.3390/pathogens5030053).
Abstract
The bronchial epithelium provides protection against pathogens from the inhaled environment through the formation of a highly-regulated barrier. In order to understand the pulmonary diseases melioidosis and tularemia caused by Burkholderia thailandensis and Fransicella tularensis, respectively, the barrier function of the human bronchial epithelium were analysed. Polarised 16HBE14o- or differentiated primary human bronchial epithelial cells (BECs) were exposed to increasing multiplicities of infection (MOI) of B. thailandensis or F. tularensis Live Vaccine Strain and barrier responses monitored over 24–72 h. Challenge of polarized BECs with either bacterial species
caused an MOI- and time-dependent increase in ionic permeability, disruption of tight junctions, and bacterial passage from the apical to the basolateral compartment. B. thailandensis was found to be more invasive than F. tularensis. Both bacterial species induced an MOI-dependent increase in TNF-α release. An increase in ionic permeability and TNF-α release was induced by B. thailandensis in differentiated BECs. Pretreatment of polarised BECs with the corticosteroid fluticasone propionate reduced bacterial-dependent increases in ionic permeability, bacterial passage, and TNF-α release.
TNF blocking antibody Enbrel® reduced bacterial passage only. BEC barrier properties are disrupted during respiratory bacterial infections and targeting with corticosteroids or anti-TNF compounds may represent a therapeutic option.
Text
Blume et al, 2016 epithelial responses to Burkholderia and Francisella.pdf
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More information
Accepted/In Press date: 26 July 2016
e-pub ahead of print date: 3 August 2016
Published date: 3 August 2016
Additional Information:
Funded by Ministry of Defence: In vitro models of the lung epithelium to study host-pathogen interactions
Keywords:
Journal Article
Organisations:
Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 398887
URI: http://eprints.soton.ac.uk/id/eprint/398887
ISSN: 2076-0817
PURE UUID: 71e164bb-40bf-4d06-8a00-7a3082abd370
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Date deposited: 04 Aug 2016 09:25
Last modified: 15 Mar 2024 03:45
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Author:
Jonathan David
Author:
Rachel E. Bell
Author:
Graeme C. Clark
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