{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:50:06Z","timestamp":1790733006423,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thematic Translational Unit Tuberculosis","award":["TTU 02.806"],"award-info":[{"award-number":["TTU 02.806"]}]},{"name":"Thematic Translational Unit Tuberculosis","award":["TTU 02.905"],"award-info":[{"award-number":["TTU 02.905"]}]},{"name":"Cologne Fortune Program","award":["473\/2020"],"award-info":[{"award-number":["473\/2020"]}]},{"name":"Cologne Clinician Scientist Program","award":["FI 773\/15-1"],"award-info":[{"award-number":["FI 773\/15-1"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["414786233"],"award-info":[{"award-number":["414786233"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["158989968"],"award-info":[{"award-number":["158989968"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"COVIM project of NaFoUniMedCovid19 network","award":["01KX2021"],"award-info":[{"award-number":["01KX2021"]}]},{"name":"Center for Molecular Medicine Cologne","award":["ZMMK-CAP8"],"award-info":[{"award-number":["ZMMK-CAP8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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-1\u03b2. Lytic cell death via gasdermin D (GSDMD), pore formation, and pyroptosis are required for IL-1\u03b2 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.<\/jats:p>","DOI":"10.3390\/v13102076","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T13:59:52Z","timestamp":1634565592000},"page":"2076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages"],"prefix":"10.3390","volume":"13","author":[{"given":"Hannah S.","family":"Eisfeld","sequence":"first","affiliation":[{"name":"Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-9897","authenticated-orcid":false,"given":"Alexander","family":"Simonis","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Winter","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Chhen","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa J.","family":"Str\u00f6h","sequence":"additional","affiliation":[{"name":"Institute of Virology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-7241","authenticated-orcid":false,"given":"Thomas","family":"Krey","sequence":"additional","affiliation":[{"name":"Institute of Virology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of Luebeck, 23562 Luebeck, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 22607 Hamburg, Germany"},{"name":"Excellence Cluster 2155 RESIST, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2962-7814","authenticated-orcid":false,"given":"Manuel","family":"Koch","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"},{"name":"Institute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian J.","family":"Theobald","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8351-2690","authenticated-orcid":false,"given":"Jan","family":"Rybniker","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","unstructured":"(2021, October 13). 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