Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19
Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens a...
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-10-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI149834 |
| _version_ | 1797634408714338304 |
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| author | Janessa Y.J. Tan Danielle E. Anderson Abhay P.S. Rathore Aled O’Neill Chinmay Kumar Mantri Wilfried A.A. Saron Cheryl Q.E. Lee Chu Wern Cui Adrian E.Z. Kang Randy Foo Shirin Kalimuddin Jenny G. Low Lena Ho Paul Tambyah Thomas W. Burke Christopher W. Woods Kuan Rong Chan Jörn Karhausen Ashley L. St. John |
| author_facet | Janessa Y.J. Tan Danielle E. Anderson Abhay P.S. Rathore Aled O’Neill Chinmay Kumar Mantri Wilfried A.A. Saron Cheryl Q.E. Lee Chu Wern Cui Adrian E.Z. Kang Randy Foo Shirin Kalimuddin Jenny G. Low Lena Ho Paul Tambyah Thomas W. Burke Christopher W. Woods Kuan Rong Chan Jörn Karhausen Ashley L. St. John |
| author_sort | Janessa Y.J. Tan |
| collection | DOAJ |
| description | Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens and often promote inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and nonhuman primates. Using a mouse model of MC deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed through detection of MC-specific proteases, including chymase, the levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention. |
| first_indexed | 2024-03-11T12:07:15Z |
| format | Article |
| id | doaj.art-0ded7096dad04c348c5c375637996e23 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:07:15Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-0ded7096dad04c348c5c375637996e232023-11-07T16:20:55ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-10-0113319Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19Janessa Y.J. TanDanielle E. AndersonAbhay P.S. RathoreAled O’NeillChinmay Kumar MantriWilfried A.A. SaronCheryl Q.E. LeeChu Wern CuiAdrian E.Z. KangRandy FooShirin KalimuddinJenny G. LowLena HoPaul TambyahThomas W. BurkeChristopher W. WoodsKuan Rong ChanJörn KarhausenAshley L. St. JohnLung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens and often promote inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and nonhuman primates. Using a mouse model of MC deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed through detection of MC-specific proteases, including chymase, the levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.https://doi.org/10.1172/JCI149834COVID-19 |
| spellingShingle | Janessa Y.J. Tan Danielle E. Anderson Abhay P.S. Rathore Aled O’Neill Chinmay Kumar Mantri Wilfried A.A. Saron Cheryl Q.E. Lee Chu Wern Cui Adrian E.Z. Kang Randy Foo Shirin Kalimuddin Jenny G. Low Lena Ho Paul Tambyah Thomas W. Burke Christopher W. Woods Kuan Rong Chan Jörn Karhausen Ashley L. St. John Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19 The Journal of Clinical Investigation COVID-19 |
| title | Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19 |
| title_full | Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19 |
| title_fullStr | Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19 |
| title_full_unstemmed | Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19 |
| title_short | Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19 |
| title_sort | mast cell activation in lungs during sars cov 2 infection associated with lung pathology and severe covid 19 |
| topic | COVID-19 |
| url | https://doi.org/10.1172/JCI149834 |
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