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Influence of hypoxia on the epithelial-pathogen interactions in the lung: implications for respiratory disease

Influence of hypoxia on the epithelial-pathogen interactions in the lung: implications for respiratory disease
Influence of hypoxia on the epithelial-pathogen interactions in the lung: implications for respiratory disease
Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies.
epithelial cells, host-pathogen interactions, hypoxia, hypoxia-inducible factor (HIF)-1, innate immunity, respiratory disease
1664-3224
Page, Lee K.
541eea0a-19ec-4326-bce2-b2931b393fbf
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Spalluto, C. Mirella
6802ad50-bc38-404f-9a19-40916425183b
Watson, Alastair
9eb79329-8d32-4ed4-b8b9-d720883e8042
Wilkinson, Thomas
8c55ebbb-e547-445c-95a1-c8bed02dd652
Page, Lee K.
541eea0a-19ec-4326-bce2-b2931b393fbf
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Spalluto, C. Mirella
6802ad50-bc38-404f-9a19-40916425183b
Watson, Alastair
9eb79329-8d32-4ed4-b8b9-d720883e8042
Wilkinson, Thomas
8c55ebbb-e547-445c-95a1-c8bed02dd652

Page, Lee K., Staples, Karl J., Spalluto, C. Mirella, Watson, Alastair and Wilkinson, Thomas (2021) Influence of hypoxia on the epithelial-pathogen interactions in the lung: implications for respiratory disease. Frontiers in Immunology, 12, [653969]. (doi:10.3389/fimmu.2021.653969).

Record type: Article

Abstract

Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies.

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Hypoxia_Review_Frontiers Revision accepted - Accepted Manuscript
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Page et al 2021 Front Immunol - Version of Record
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Accepted/In Press date: 9 March 2021
Published date: 24 March 2021
Keywords: epithelial cells, host-pathogen interactions, hypoxia, hypoxia-inducible factor (HIF)-1, innate immunity, respiratory disease

Identifiers

Local EPrints ID: 447722
URI: http://eprints.soton.ac.uk/id/eprint/447722
ISSN: 1664-3224
PURE UUID: ab76b7fa-d1f7-4c16-81c1-5653971aec12
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

Catalogue record

Date deposited: 18 Mar 2021 17:57
Last modified: 26 Nov 2021 02:51

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Contributors

Author: Lee K. Page
Author: Karl J. Staples ORCID iD
Author: C. Mirella Spalluto
Author: Alastair Watson

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