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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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Autores principales: Eisfeld, Hannah S., Simonis, Alexander, Winter, Sandra, Chhen, Jason, Ströh, Luisa J., Krey, Thomas, Koch, Manuel, Theobald, Sebastian J., Rybniker, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538122/
https://www.ncbi.nlm.nih.gov/pubmed/34696506
http://dx.doi.org/10.3390/v13102076
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author Eisfeld, Hannah S.
Simonis, Alexander
Winter, Sandra
Chhen, Jason
Ströh, Luisa J.
Krey, Thomas
Koch, Manuel
Theobald, Sebastian J.
Rybniker, Jan
author_facet Eisfeld, Hannah S.
Simonis, Alexander
Winter, Sandra
Chhen, Jason
Ströh, Luisa J.
Krey, Thomas
Koch, Manuel
Theobald, Sebastian J.
Rybniker, Jan
author_sort Eisfeld, Hannah S.
collection PubMed
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.
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spelling pubmed-85381222021-10-24 Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages Eisfeld, Hannah S. Simonis, Alexander Winter, Sandra Chhen, Jason Ströh, Luisa J. Krey, Thomas Koch, Manuel Theobald, Sebastian J. Rybniker, Jan Viruses Article 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. MDPI 2021-10-15 /pmc/articles/PMC8538122/ /pubmed/34696506 http://dx.doi.org/10.3390/v13102076 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eisfeld, Hannah S.
Simonis, Alexander
Winter, Sandra
Chhen, Jason
Ströh, Luisa J.
Krey, Thomas
Koch, Manuel
Theobald, Sebastian J.
Rybniker, Jan
Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in 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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538122/
https://www.ncbi.nlm.nih.gov/pubmed/34696506
http://dx.doi.org/10.3390/v13102076
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