tetano
Editor, Senior Moderator
J Clin Invest
. 2023 Aug 10;e149834.
doi: 10.1172/JCI149834. Online ahead of print. Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19
Janessa Yan Jun Tan[SUP] 1 [/SUP], Danielle E Anderson[SUP] 2 [/SUP], Abhay Ps Rathore[SUP] 3 [/SUP], Aled O'Neill[SUP] 1 [/SUP], Chinmay Kumar Mantri[SUP] 1 [/SUP], Wilfried Aa Saron[SUP] 1 [/SUP], Cheryl Qe Lee[SUP] 4 [/SUP], Wern Cui Chu[SUP] 4 [/SUP], Adrian Ez Kang[SUP] 1 [/SUP], Randy Foo[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 5 [/SUP], Jenny G Low[SUP] 5 [/SUP], Lena Ho[SUP] 4 [/SUP], Paul Tambyah[SUP] 6 [/SUP], Thomas W Burke[SUP] 7 [/SUP], Christopher W Woods[SUP] 7 [/SUP], Kuan Rong Chan[SUP] 1 [/SUP], Joern Karhausen[SUP] 8 [/SUP], Ashley L St John[SUP] 1 [/SUP]
Affiliations
Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients 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, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human 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, 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.
. 2023 Aug 10;e149834.
doi: 10.1172/JCI149834. Online ahead of print. Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19
Janessa Yan Jun Tan[SUP] 1 [/SUP], Danielle E Anderson[SUP] 2 [/SUP], Abhay Ps Rathore[SUP] 3 [/SUP], Aled O'Neill[SUP] 1 [/SUP], Chinmay Kumar Mantri[SUP] 1 [/SUP], Wilfried Aa Saron[SUP] 1 [/SUP], Cheryl Qe Lee[SUP] 4 [/SUP], Wern Cui Chu[SUP] 4 [/SUP], Adrian Ez Kang[SUP] 1 [/SUP], Randy Foo[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 5 [/SUP], Jenny G Low[SUP] 5 [/SUP], Lena Ho[SUP] 4 [/SUP], Paul Tambyah[SUP] 6 [/SUP], Thomas W Burke[SUP] 7 [/SUP], Christopher W Woods[SUP] 7 [/SUP], Kuan Rong Chan[SUP] 1 [/SUP], Joern Karhausen[SUP] 8 [/SUP], Ashley L St John[SUP] 1 [/SUP]
Affiliations
- PMID: 37561585
- DOI: 10.1172/JCI149834
Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients 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, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human 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, 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.