SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue
Two years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune–inflammatory pathways that p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/11/1390 |
| _version_ | 1797464233611362304 |
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| author | Bianca Vezzani Margherita Neri Stefano D’Errico Alberto Papi Marco Contoli Carlotta Giorgi |
| author_facet | Bianca Vezzani Margherita Neri Stefano D’Errico Alberto Papi Marco Contoli Carlotta Giorgi |
| author_sort | Bianca Vezzani |
| collection | DOAJ |
| description | Two years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune–inflammatory pathways that prompt the manifestation of the disease to identify a novel potential target for pharmacological intervention. In this context, the characterization of the main players in the SARS-CoV-2-induced cytokine storm is mandatory. To date, the most characterized have been IL-6 and the class I and II interferons, while less is known about the proinflammatory cytokine IL-1β and class III interferons. Here, we report a preliminary study aimed at the characterization of the lung inflammatory context in COVID-19 patients, with a special focus on IFN-λ and IL-1β. By investigating IFN and inflammatory cytokine patterns by IHC in 10 deceased patients due to COVID-19 infection, compared to 10 control subjects, we reveal that while IFN-β production was increased in COVID-19 patients, IFN-λ was almost abolished. At the same time, the levels of IL-1β were dramatically improved, while IL-6 lung levels seem to be unaffected by the infection. Our findings highlight a central role of IL-1β in prompting lung inflammation after SARS-CoV-2 infection. Together, we show that IFN-λ is negatively affected by viral infection, supporting the idea that IFN-λ administration together with the pharmaceutical blockage of IL-1β represents a promising approach to revert the COVID-19-induced cytokine storm. |
| first_indexed | 2024-03-09T18:05:20Z |
| format | Article |
| id | doaj.art-99c52d2764af4bc5a8af3c882bea3165 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T18:05:20Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-99c52d2764af4bc5a8af3c882bea31652023-11-24T09:34:57ZengMDPI AGPathogens2076-08172022-11-011111139010.3390/pathogens11111390SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung TissueBianca Vezzani0Margherita Neri1Stefano D’Errico2Alberto Papi3Marco Contoli4Carlotta Giorgi5Department of Medical Sciences, Section of Experimental Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Public Health Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medicine, Surgery and Health, University of Trieste, 34149 Trieste, ItalyRespiratory Medicine, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyRespiratory Medicine, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Experimental Medicine, University of Ferrara, 44121 Ferrara, ItalyTwo years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune–inflammatory pathways that prompt the manifestation of the disease to identify a novel potential target for pharmacological intervention. In this context, the characterization of the main players in the SARS-CoV-2-induced cytokine storm is mandatory. To date, the most characterized have been IL-6 and the class I and II interferons, while less is known about the proinflammatory cytokine IL-1β and class III interferons. Here, we report a preliminary study aimed at the characterization of the lung inflammatory context in COVID-19 patients, with a special focus on IFN-λ and IL-1β. By investigating IFN and inflammatory cytokine patterns by IHC in 10 deceased patients due to COVID-19 infection, compared to 10 control subjects, we reveal that while IFN-β production was increased in COVID-19 patients, IFN-λ was almost abolished. At the same time, the levels of IL-1β were dramatically improved, while IL-6 lung levels seem to be unaffected by the infection. Our findings highlight a central role of IL-1β in prompting lung inflammation after SARS-CoV-2 infection. Together, we show that IFN-λ is negatively affected by viral infection, supporting the idea that IFN-λ administration together with the pharmaceutical blockage of IL-1β represents a promising approach to revert the COVID-19-induced cytokine storm.https://www.mdpi.com/2076-0817/11/11/1390SARS-CoV-2COVID-19IFN-λIL-1βIL-6lungs |
| spellingShingle | Bianca Vezzani Margherita Neri Stefano D’Errico Alberto Papi Marco Contoli Carlotta Giorgi SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue Pathogens SARS-CoV-2 COVID-19 IFN-λ IL-1β IL-6 lungs |
| title | SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue |
| title_full | SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue |
| title_fullStr | SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue |
| title_full_unstemmed | SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue |
| title_short | SARS-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue |
| title_sort | sars cov 2 infection prompts il 1β mediated inflammation and reduces ifn λ expression in human lung tissue |
| topic | SARS-CoV-2 COVID-19 IFN-λ IL-1β IL-6 lungs |
| url | https://www.mdpi.com/2076-0817/11/11/1390 |
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