Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers
Abstract Background Respiratory syncytial virus (RSV) induces exacerbations of chronic obstructive pulmonary disease (COPD) that are critical for disease progression and burden. COPD subjects have an increased susceptibility to viral respiratory infections. We aimed to identify underlying systemic i...
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BMC
2025-06-01
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| Online Access: | https://doi.org/10.1186/s10020-025-01277-4 |
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| author | Sarah D. Yanik Kaschin Jamal Jameel Simon Rohde Paul Bürger Eike Bülthoff Thomas Grunwald Juliane Kronsbein Andrea Koch Michael R. Edwards Matthias Tenbusch Jürgen Knobloch |
| author_facet | Sarah D. Yanik Kaschin Jamal Jameel Simon Rohde Paul Bürger Eike Bülthoff Thomas Grunwald Juliane Kronsbein Andrea Koch Michael R. Edwards Matthias Tenbusch Jürgen Knobloch |
| author_sort | Sarah D. Yanik |
| collection | DOAJ |
| description | Abstract Background Respiratory syncytial virus (RSV) induces exacerbations of chronic obstructive pulmonary disease (COPD) that are critical for disease progression and burden. COPD subjects have an increased susceptibility to viral respiratory infections. We aimed to identify underlying systemic immune pathologies that could be used as drug targets to reduce exacerbations. Methods Peripheral blood mononuclear cells were isolated from 16 healthy never smokers, 17 current smokers without airflow limitation, and 17 COPD subjects. The cells were cultured and infected with RSV for 24 h or seven days. IFNα, T-cell- and inflammatory cytokines, the expression of interferon-stimulating genes (ISGs), and virus load in supernatants were measured by ELISA or real-time PCR, respectively. Data were compared between the three patient groups. Results RSV induced CCL2, CCL5, IFNα, IFNγ, IL1-β, IL-6, IL-8, and TNFα but not IL-4, IL-5, IL-17, GM-CSF, and TGFβ. CCL2 was unchanged between the groups. All other cytokines were either increased or produced for a longer period of time in COPD but were reduced or not produced at all in smokers. Virus copy numbers were increased in COPD but reduced in smokers. RSV induced MxA, OAS, and Viperin expression with differences between the groups. Conclusion Circulating immune cells in COPD might cause cytokine overproduction in response to RSV after recruitment to the site of infection and might contribute to the increase in inflammation in exacerbations. This might be explained by differences in RSV replication efficacy and ISG expression. We provide first indication for ISGs and circulating cells as drug targets to reduce or prevent exacerbations. |
| format | Article |
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| issn | 1528-3658 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-b94c7d3cf3bc4de8b5e998539ea35ed92025-08-20T02:06:19ZengBMCMolecular Medicine1528-36582025-06-0131111110.1186/s10020-025-01277-4Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokersSarah D. Yanik0Kaschin Jamal Jameel1Simon Rohde2Paul Bürger3Eike Bülthoff4Thomas Grunwald5Juliane Kronsbein6Andrea Koch7Michael R. Edwards8Matthias Tenbusch9Jürgen Knobloch10Medical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumMedical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumMedical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumMedical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumMedical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumFraunhofer Institute for Cell Therapy and ImmunologyMedical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumJohannes Kepler Universität (JKU) und Kepler Universitätsklinikum (KUK) Linz; MC IIINational Heart and Lung Institute, Imperial CollegeInstitute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich- Alexander-Universität (FAU) Erlangen-NürnbergMedical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Ruhr-University BochumAbstract Background Respiratory syncytial virus (RSV) induces exacerbations of chronic obstructive pulmonary disease (COPD) that are critical for disease progression and burden. COPD subjects have an increased susceptibility to viral respiratory infections. We aimed to identify underlying systemic immune pathologies that could be used as drug targets to reduce exacerbations. Methods Peripheral blood mononuclear cells were isolated from 16 healthy never smokers, 17 current smokers without airflow limitation, and 17 COPD subjects. The cells were cultured and infected with RSV for 24 h or seven days. IFNα, T-cell- and inflammatory cytokines, the expression of interferon-stimulating genes (ISGs), and virus load in supernatants were measured by ELISA or real-time PCR, respectively. Data were compared between the three patient groups. Results RSV induced CCL2, CCL5, IFNα, IFNγ, IL1-β, IL-6, IL-8, and TNFα but not IL-4, IL-5, IL-17, GM-CSF, and TGFβ. CCL2 was unchanged between the groups. All other cytokines were either increased or produced for a longer period of time in COPD but were reduced or not produced at all in smokers. Virus copy numbers were increased in COPD but reduced in smokers. RSV induced MxA, OAS, and Viperin expression with differences between the groups. Conclusion Circulating immune cells in COPD might cause cytokine overproduction in response to RSV after recruitment to the site of infection and might contribute to the increase in inflammation in exacerbations. This might be explained by differences in RSV replication efficacy and ISG expression. We provide first indication for ISGs and circulating cells as drug targets to reduce or prevent exacerbations.https://doi.org/10.1186/s10020-025-01277-4RSVCOPDExacerbationCirculating immune cellsCytokine overproduction |
| spellingShingle | Sarah D. Yanik Kaschin Jamal Jameel Simon Rohde Paul Bürger Eike Bülthoff Thomas Grunwald Juliane Kronsbein Andrea Koch Michael R. Edwards Matthias Tenbusch Jürgen Knobloch Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers Molecular Medicine RSV COPD Exacerbation Circulating immune cells Cytokine overproduction |
| title | Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers |
| title_full | Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers |
| title_fullStr | Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers |
| title_full_unstemmed | Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers |
| title_short | Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers |
| title_sort | cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in copd but suppressed in non copd tobacco smokers |
| topic | RSV COPD Exacerbation Circulating immune cells Cytokine overproduction |
| url | https://doi.org/10.1186/s10020-025-01277-4 |
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