Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection
Cystic fibrosis (CF) lung disease is aggravated by recurrent and ultimately chronic bacterial infections. One of the key pathogens in adult CF lung disease is P. aeruginosa (PA). In addition to bacteria, respiratory viral infections are suggested to trigger pulmonary exacerbations in CF. To date, li...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.846828/full |
| _version_ | 1818329518572568576 |
|---|---|
| author | Adrian Endres Christian Hügel Helena Boland Michael Hogardt Ralf Schubert Danny Jonigk Danny Jonigk Peter Braubach Peter Braubach Gernot Rohde Carla Bellinghausen |
| author_facet | Adrian Endres Christian Hügel Helena Boland Michael Hogardt Ralf Schubert Danny Jonigk Danny Jonigk Peter Braubach Peter Braubach Gernot Rohde Carla Bellinghausen |
| author_sort | Adrian Endres |
| collection | DOAJ |
| description | Cystic fibrosis (CF) lung disease is aggravated by recurrent and ultimately chronic bacterial infections. One of the key pathogens in adult CF lung disease is P. aeruginosa (PA). In addition to bacteria, respiratory viral infections are suggested to trigger pulmonary exacerbations in CF. To date, little is known on how chronic infections with PA influence susceptibility and response to viral infection. We investigated the interactions between PA, human rhinovirus (HRV) and the airway epithelium in a model of chronic PA infection using differentiated primary bronchial epithelial cells (pBECs) and clinical PA isolates obtained from the respiratory sample of a CF patient. Cells were repeatedly infected with either a mucoid or a non-mucoid PA isolate for 16 days to simulate chronic infection, and subsequently co-infected with HRV. Key cytokines and viral RNA were quantified by cytometric bead array, ELISA and qPCR. Proteolytic degradation of IL-6 was analyzed by Western Blots. Barrier function was assessed by permeability tests and transepithelial electric resistance measurements. Virus infection stimulated the production of inflammatory and antiviral mediators, including interleukin (IL)-6, CXCL-8, tumor necrosis factor (TNF)-α, and type I/III interferons. Co-infection with a non-mucoid PA isolate increased IL-1β protein concentrations (28.88 pg/ml vs. 6.10 pg/ml), but in contrast drastically diminished levels of IL-6 protein (53.17 pg/ml vs. 2301.33 pg/ml) compared to virus infection alone. Conditioned medium obtained from co-infections with a non-mucoid PA isolate and HRV was able to rapidly degrade recombinant IL-6 in a serine protease-dependent manner, whereas medium from individual infections or co-infections with a mucoid isolate had no such effect. After co-infection with HRV and the non-mucoid PA isolate, we detected lower mRNA levels of Forkhead box J1 (FOXJ1) and Cilia Apical Structure Protein (SNTN), markers of epithelial cell differentiation to ciliated cells. Moreover, epithelial permeability was increased and barrier function compromised compared to single infections. These data show that PA infection can influence the response of bronchial epithelial cells to viral infection. Altered innate immune responses and compromised epithelial barrier function may contribute to an aggravated course of viral infection in PA-infected airways. |
| first_indexed | 2024-12-13T12:49:20Z |
| format | Article |
| id | doaj.art-fc242d79f65249b0be12fc2560df074d |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T12:49:20Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-fc242d79f65249b0be12fc2560df074d2022-12-21T23:45:24ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-02-011210.3389/fcimb.2022.846828846828Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus InfectionAdrian Endres0Christian Hügel1Helena Boland2Michael Hogardt3Ralf Schubert4Danny Jonigk5Danny Jonigk6Peter Braubach7Peter Braubach8Gernot Rohde9Carla Bellinghausen10Department of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyConsiliary Laboratory on Cystic Fibrosis Bacteriology, Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyInstitute for Pathology, Hannover Medical School, Hannover, GermanyGerman Center for Lung Research (DZL), Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), Hannover, GermanyInstitute for Pathology, Hannover Medical School, Hannover, GermanyGerman Center for Lung Research (DZL), Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), Hannover, GermanyDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyCystic fibrosis (CF) lung disease is aggravated by recurrent and ultimately chronic bacterial infections. One of the key pathogens in adult CF lung disease is P. aeruginosa (PA). In addition to bacteria, respiratory viral infections are suggested to trigger pulmonary exacerbations in CF. To date, little is known on how chronic infections with PA influence susceptibility and response to viral infection. We investigated the interactions between PA, human rhinovirus (HRV) and the airway epithelium in a model of chronic PA infection using differentiated primary bronchial epithelial cells (pBECs) and clinical PA isolates obtained from the respiratory sample of a CF patient. Cells were repeatedly infected with either a mucoid or a non-mucoid PA isolate for 16 days to simulate chronic infection, and subsequently co-infected with HRV. Key cytokines and viral RNA were quantified by cytometric bead array, ELISA and qPCR. Proteolytic degradation of IL-6 was analyzed by Western Blots. Barrier function was assessed by permeability tests and transepithelial electric resistance measurements. Virus infection stimulated the production of inflammatory and antiviral mediators, including interleukin (IL)-6, CXCL-8, tumor necrosis factor (TNF)-α, and type I/III interferons. Co-infection with a non-mucoid PA isolate increased IL-1β protein concentrations (28.88 pg/ml vs. 6.10 pg/ml), but in contrast drastically diminished levels of IL-6 protein (53.17 pg/ml vs. 2301.33 pg/ml) compared to virus infection alone. Conditioned medium obtained from co-infections with a non-mucoid PA isolate and HRV was able to rapidly degrade recombinant IL-6 in a serine protease-dependent manner, whereas medium from individual infections or co-infections with a mucoid isolate had no such effect. After co-infection with HRV and the non-mucoid PA isolate, we detected lower mRNA levels of Forkhead box J1 (FOXJ1) and Cilia Apical Structure Protein (SNTN), markers of epithelial cell differentiation to ciliated cells. Moreover, epithelial permeability was increased and barrier function compromised compared to single infections. These data show that PA infection can influence the response of bronchial epithelial cells to viral infection. Altered innate immune responses and compromised epithelial barrier function may contribute to an aggravated course of viral infection in PA-infected airways.https://www.frontiersin.org/articles/10.3389/fcimb.2022.846828/fullco-infectioncystic fibrosisbronchial epitheliumrespiratory infectionsrhinovirusPseudomonas aeruginosa |
| spellingShingle | Adrian Endres Christian Hügel Helena Boland Michael Hogardt Ralf Schubert Danny Jonigk Danny Jonigk Peter Braubach Peter Braubach Gernot Rohde Carla Bellinghausen Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection Frontiers in Cellular and Infection Microbiology co-infection cystic fibrosis bronchial epithelium respiratory infections rhinovirus Pseudomonas aeruginosa |
| title | Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection |
| title_full | Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection |
| title_fullStr | Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection |
| title_full_unstemmed | Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection |
| title_short | Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection |
| title_sort | pseudomonas aeruginosa affects airway epithelial response and barrier function during rhinovirus infection |
| topic | co-infection cystic fibrosis bronchial epithelium respiratory infections rhinovirus Pseudomonas aeruginosa |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.846828/full |
| work_keys_str_mv | AT adrianendres pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT christianhugel pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT helenaboland pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT michaelhogardt pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT ralfschubert pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT dannyjonigk pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT dannyjonigk pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT peterbraubach pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT peterbraubach pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT gernotrohde pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection AT carlabellinghausen pseudomonasaeruginosaaffectsairwayepithelialresponseandbarrierfunctionduringrhinovirusinfection |