Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores
Summary: Viral sensing in myeloid cells involves inflammasome activation leading to gasdermin pore formation, cytokine release, and cell death. However, less is known about viral sensing in barrier epithelial cells, which are critical to the innate immune response to RNA viruses. Here, we show that...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223017753 |
| _version_ | 1797731035912339456 |
|---|---|
| author | Coralie Guy Marcin Baran Pau Ribó-Molina Bernadette G. van den Hoogen Andrew G. Bowie |
| author_facet | Coralie Guy Marcin Baran Pau Ribó-Molina Bernadette G. van den Hoogen Andrew G. Bowie |
| author_sort | Coralie Guy |
| collection | DOAJ |
| description | Summary: Viral sensing in myeloid cells involves inflammasome activation leading to gasdermin pore formation, cytokine release, and cell death. However, less is known about viral sensing in barrier epithelial cells, which are critical to the innate immune response to RNA viruses. Here, we show that poly(I:C), a mimic of viral dsRNA, is sensed by NLRP1 in human bronchial epithelial cells, leading to inflammasome-dependent gasdermin D (GSDMD) pore formation via caspase-1. DsRNA also stimulated a parallel sensing pathway via PKR which activated caspase-3 to cleave gasdermin E (GSDME) to form active pores. Influenza A virus (IAV) infection of cells caused GSDME activation, cytokine release, and cell death, in a PKR-dependent but NLRP1-independent manner, involving caspase-8 and caspase-3. Suppression of GSDMD and GSDME expression increased IAV replication. These data clarify mechanisms of gasdermin cleavage in response to viral sensing and reveal that gasdermin pore formation is intrinsically antiviral in human epithelial cells. |
| first_indexed | 2024-03-12T11:52:34Z |
| format | Article |
| id | doaj.art-a607ac954d334d5f9f7983df4f8ad153 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T11:52:34Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-a607ac954d334d5f9f7983df4f8ad1532023-08-31T05:03:36ZengElsevieriScience2589-00422023-09-01269107698Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E poresCoralie Guy0Marcin Baran1Pau Ribó-Molina2Bernadette G. van den Hoogen3Andrew G. Bowie4School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, IrelandDepartment of Viroscience, Erasmus Medical Center, Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus Medical Center, Rotterdam, the NetherlandsSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Corresponding authorSummary: Viral sensing in myeloid cells involves inflammasome activation leading to gasdermin pore formation, cytokine release, and cell death. However, less is known about viral sensing in barrier epithelial cells, which are critical to the innate immune response to RNA viruses. Here, we show that poly(I:C), a mimic of viral dsRNA, is sensed by NLRP1 in human bronchial epithelial cells, leading to inflammasome-dependent gasdermin D (GSDMD) pore formation via caspase-1. DsRNA also stimulated a parallel sensing pathway via PKR which activated caspase-3 to cleave gasdermin E (GSDME) to form active pores. Influenza A virus (IAV) infection of cells caused GSDME activation, cytokine release, and cell death, in a PKR-dependent but NLRP1-independent manner, involving caspase-8 and caspase-3. Suppression of GSDMD and GSDME expression increased IAV replication. These data clarify mechanisms of gasdermin cleavage in response to viral sensing and reveal that gasdermin pore formation is intrinsically antiviral in human epithelial cells.http://www.sciencedirect.com/science/article/pii/S2589004223017753ImmunologyVirology |
| spellingShingle | Coralie Guy Marcin Baran Pau Ribó-Molina Bernadette G. van den Hoogen Andrew G. Bowie Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores iScience Immunology Virology |
| title | Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores |
| title_full | Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores |
| title_fullStr | Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores |
| title_full_unstemmed | Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores |
| title_short | Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores |
| title_sort | viral sensing by epithelial cells involves pkr and caspase 3 dependent generation of gasdermin e pores |
| topic | Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223017753 |
| work_keys_str_mv | AT coralieguy viralsensingbyepithelialcellsinvolvespkrandcaspase3dependentgenerationofgasderminepores AT marcinbaran viralsensingbyepithelialcellsinvolvespkrandcaspase3dependentgenerationofgasderminepores AT pauribomolina viralsensingbyepithelialcellsinvolvespkrandcaspase3dependentgenerationofgasderminepores AT bernadettegvandenhoogen viralsensingbyepithelialcellsinvolvespkrandcaspase3dependentgenerationofgasderminepores AT andrewgbowie viralsensingbyepithelialcellsinvolvespkrandcaspase3dependentgenerationofgasderminepores |