LPS binding protein and activation signatures are upregulated during asthma exacerbations in children
Abstract Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways re...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02478-3 |
| _version_ | 1797778680161763328 |
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| author | Anya C. Jones Jonatan Leffler Ingrid A. Laing Joelene Bizzintino Siew-Kim Khoo Peter N. LeSouef Peter D. Sly Patrick G. Holt Deborah H. Strickland Anthony Bosco |
| author_facet | Anya C. Jones Jonatan Leffler Ingrid A. Laing Joelene Bizzintino Siew-Kim Khoo Peter N. LeSouef Peter D. Sly Patrick G. Holt Deborah H. Strickland Anthony Bosco |
| author_sort | Anya C. Jones |
| collection | DOAJ |
| description | Abstract Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children (n = 19) during acute virus-associated exacerbations and later during convalescence. Systems level analyses were employed to identify coexpression networks and infer the drivers of these networks, and validation was subsequently obtained via independent samples from asthmatic children. During exacerbations, PBMC exhibited significant changes in immune cell abundance and upregulation of complex interlinked networks of coexpressed genes. These were associated with priming of innate immunity, inflammatory and remodelling functions. We identified activation signatures downstream of bacterial LPS, glucocorticoids and TGFB1. We also confirmed that LPS binding protein was upregulated at the protein-level in plasma. Multiple gene networks known to be involved positively or negatively in asthma pathogenesis, are upregulated in circulating PBMC during acute exacerbations, supporting the hypothesis that systemic pre-programming of potentially pathogenic as well as protective functions of circulating immune cells preceeds migration into the airways. Enhanced sensitivity to LPS is likely to modulate the severity of acute asthma exacerbations through exposure to environmental LPS. |
| first_indexed | 2024-03-12T23:20:57Z |
| format | Article |
| id | doaj.art-18ac5eb4bd4b4257b8ceb0da32978369 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-12T23:20:57Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-18ac5eb4bd4b4257b8ceb0da329783692023-07-16T11:25:32ZengBMCRespiratory Research1465-993X2023-07-0124111210.1186/s12931-023-02478-3LPS binding protein and activation signatures are upregulated during asthma exacerbations in childrenAnya C. Jones0Jonatan Leffler1Ingrid A. Laing2Joelene Bizzintino3Siew-Kim Khoo4Peter N. LeSouef5Peter D. Sly6Patrick G. Holt7Deborah H. Strickland8Anthony Bosco9Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaWal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaWal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaWal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaWal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaUWA Medical School, University of Western AustraliaChild Health Research Centre, The University of QueenslandWal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaWal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western AustraliaAsthma & Airway Disease Research Center, The BIO5 Institute, The University of ArizonaAbstract Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children (n = 19) during acute virus-associated exacerbations and later during convalescence. Systems level analyses were employed to identify coexpression networks and infer the drivers of these networks, and validation was subsequently obtained via independent samples from asthmatic children. During exacerbations, PBMC exhibited significant changes in immune cell abundance and upregulation of complex interlinked networks of coexpressed genes. These were associated with priming of innate immunity, inflammatory and remodelling functions. We identified activation signatures downstream of bacterial LPS, glucocorticoids and TGFB1. We also confirmed that LPS binding protein was upregulated at the protein-level in plasma. Multiple gene networks known to be involved positively or negatively in asthma pathogenesis, are upregulated in circulating PBMC during acute exacerbations, supporting the hypothesis that systemic pre-programming of potentially pathogenic as well as protective functions of circulating immune cells preceeds migration into the airways. Enhanced sensitivity to LPS is likely to modulate the severity of acute asthma exacerbations through exposure to environmental LPS.https://doi.org/10.1186/s12931-023-02478-3Atopic asthmaNetwork analysisBulk RNA-SeqPeripheral bloodLPSTGFB1 |
| spellingShingle | Anya C. Jones Jonatan Leffler Ingrid A. Laing Joelene Bizzintino Siew-Kim Khoo Peter N. LeSouef Peter D. Sly Patrick G. Holt Deborah H. Strickland Anthony Bosco LPS binding protein and activation signatures are upregulated during asthma exacerbations in children Respiratory Research Atopic asthma Network analysis Bulk RNA-Seq Peripheral blood LPS TGFB1 |
| title | LPS binding protein and activation signatures are upregulated during asthma exacerbations in children |
| title_full | LPS binding protein and activation signatures are upregulated during asthma exacerbations in children |
| title_fullStr | LPS binding protein and activation signatures are upregulated during asthma exacerbations in children |
| title_full_unstemmed | LPS binding protein and activation signatures are upregulated during asthma exacerbations in children |
| title_short | LPS binding protein and activation signatures are upregulated during asthma exacerbations in children |
| title_sort | lps binding protein and activation signatures are upregulated during asthma exacerbations in children |
| topic | Atopic asthma Network analysis Bulk RNA-Seq Peripheral blood LPS TGFB1 |
| url | https://doi.org/10.1186/s12931-023-02478-3 |
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