Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages
Infections with viral pathogens are widespread and can cause a variety of different diseases. In-depth knowledge about viral triggers initiating an immune response is necessary to decipher viral pathogenesis. Inflammasomes, as part of the innate immune system, can be activated by viral pathogens. Ho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/10/2076 |
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| author | Hannah S. Eisfeld Alexander Simonis Sandra Winter Jason Chhen Luisa J. Ströh Thomas Krey Manuel Koch Sebastian J. Theobald Jan Rybniker |
| author_facet | Hannah S. Eisfeld Alexander Simonis Sandra Winter Jason Chhen Luisa J. Ströh Thomas Krey Manuel Koch Sebastian J. Theobald Jan Rybniker |
| author_sort | Hannah S. Eisfeld |
| collection | DOAJ |
| description | Infections with viral pathogens are widespread and can cause a variety of different diseases. In-depth knowledge about viral triggers initiating an immune response is necessary to decipher viral pathogenesis. Inflammasomes, as part of the innate immune system, can be activated by viral pathogens. However, viral structural components responsible for inflammasome activation remain largely unknown. Here we analyzed glycoproteins derived from SARS-CoV-1/2, HCMV and HCV, required for viral entry and fusion, as potential triggers of NLRP3 inflammasome activation and pyroptosis in THP-1 macrophages. All tested glycoproteins were able to potently induce NLRP3 inflammasome activation, indicated by ASC-SPECK formation and secretion of cleaved IL-1β. Lytic cell death via gasdermin D (GSDMD), pore formation, and pyroptosis are required for IL-1β release. As a hallmark of pyroptosis, we were able to detect cleavage of GSDMD and, correspondingly, cell death in THP-1 macrophages. CRISPR-Cas9 knockout of NLRP3 and GSDMD in THP-1 macrophages confirmed and strongly support the evidence that viral glycoproteins can act as innate immunity triggers. With our study, we decipher key mechanisms of viral pathogenesis by showing that viral glycoproteins potently induce innate immune responses. These insights could be beneficial in vaccine development and provide new impulses for the investigation of vaccine-induced innate immunity. |
| first_indexed | 2024-03-10T06:08:13Z |
| format | Article |
| id | doaj.art-2339656ddf0643ccafee7175c27589c0 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T06:08:13Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-2339656ddf0643ccafee7175c27589c02023-11-22T20:20:25ZengMDPI AGViruses1999-49152021-10-011310207610.3390/v13102076Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in MacrophagesHannah S. Eisfeld0Alexander Simonis1Sandra Winter2Jason Chhen3Luisa J. Ströh4Thomas Krey5Manuel Koch6Sebastian J. Theobald7Jan Rybniker8Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyInstitute of Virology, Hannover Medical School, 30625 Hannover, GermanyInstitute of Virology, Hannover Medical School, 30625 Hannover, GermanyCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyInfections with viral pathogens are widespread and can cause a variety of different diseases. In-depth knowledge about viral triggers initiating an immune response is necessary to decipher viral pathogenesis. Inflammasomes, as part of the innate immune system, can be activated by viral pathogens. However, viral structural components responsible for inflammasome activation remain largely unknown. Here we analyzed glycoproteins derived from SARS-CoV-1/2, HCMV and HCV, required for viral entry and fusion, as potential triggers of NLRP3 inflammasome activation and pyroptosis in THP-1 macrophages. All tested glycoproteins were able to potently induce NLRP3 inflammasome activation, indicated by ASC-SPECK formation and secretion of cleaved IL-1β. Lytic cell death via gasdermin D (GSDMD), pore formation, and pyroptosis are required for IL-1β release. As a hallmark of pyroptosis, we were able to detect cleavage of GSDMD and, correspondingly, cell death in THP-1 macrophages. CRISPR-Cas9 knockout of NLRP3 and GSDMD in THP-1 macrophages confirmed and strongly support the evidence that viral glycoproteins can act as innate immunity triggers. With our study, we decipher key mechanisms of viral pathogenesis by showing that viral glycoproteins potently induce innate immune responses. These insights could be beneficial in vaccine development and provide new impulses for the investigation of vaccine-induced innate immunity.https://www.mdpi.com/1999-4915/13/10/2076NLRP3IL-1βpyroptosisviral glycoproteinsinnate immunitymacrophages |
| spellingShingle | Hannah S. Eisfeld Alexander Simonis Sandra Winter Jason Chhen Luisa J. Ströh Thomas Krey Manuel Koch Sebastian J. Theobald Jan Rybniker Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages Viruses NLRP3 IL-1β pyroptosis viral glycoproteins innate immunity macrophages |
| title | Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages |
| title_full | Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages |
| title_fullStr | Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages |
| title_full_unstemmed | Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages |
| title_short | Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages |
| title_sort | viral glycoproteins induce nlrp3 inflammasome activation and pyroptosis in macrophages |
| topic | NLRP3 IL-1β pyroptosis viral glycoproteins innate immunity macrophages |
| url | https://www.mdpi.com/1999-4915/13/10/2076 |
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