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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-08-01
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| Series: | Pathogens |
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| Online Access: | http://www.mdpi.com/2076-0817/5/3/53 |
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| author | Cornelia Blume Jonathan David Rachel E. Bell Jay R. Laver Robert C. Read Graeme C. Clark Donna E. Davies Emily J. Swindle |
| author_facet | Cornelia Blume Jonathan David Rachel E. Bell Jay R. Laver Robert C. Read Graeme C. Clark Donna E. Davies Emily J. Swindle |
| author_sort | Cornelia Blume |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T17:58:05Z |
| format | Article |
| id | doaj.art-cd648c8173fd4a08bd507ec171e16d99 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-04-11T17:58:05Z |
| publishDate | 2016-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-cd648c8173fd4a08bd507ec171e16d992022-12-22T04:10:36ZengMDPI AGPathogens2076-08172016-08-01535310.3390/pathogens5030053pathogens5030053Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial InfectionsCornelia Blume0Jonathan David1Rachel E. Bell2Jay R. Laver3Robert C. Read4Graeme C. Clark5Donna E. Davies6Emily J. Swindle7Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UKDefence Science and Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UKDefence Science and Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UKAcademic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UKAcademic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UKDefence Science and Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UKAcademic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UKAcademic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UKThe 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.http://www.mdpi.com/2076-0817/5/3/53airway epitheliumbacterial infectionBurkholderia thailandensisFransicella tularensisbarrier functionsbacterial passagefluticasone propionate |
| spellingShingle | Cornelia Blume Jonathan David Rachel E. Bell Jay R. Laver Robert C. Read Graeme C. Clark Donna E. Davies Emily J. Swindle Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections Pathogens airway epithelium bacterial infection Burkholderia thailandensis Fransicella tularensis barrier functions bacterial passage fluticasone propionate |
| title | Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections |
| title_full | Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections |
| title_fullStr | Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections |
| title_full_unstemmed | Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections |
| title_short | Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections |
| title_sort | modulation of human airway barrier functions during burkholderia thailandensis and francisella tularensis infection running title airway barrier functions during bacterial infections |
| topic | airway epithelium bacterial infection Burkholderia thailandensis Fransicella tularensis barrier functions bacterial passage fluticasone propionate |
| url | http://www.mdpi.com/2076-0817/5/3/53 |
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