Apoptotic signaling clears engineered Salmonella in an organ-specific manner
Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compared to pyroptosis in defense against an intracellular...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89210 |
| _version_ | 1797402125218611200 |
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| author | Taylor J Abele Zachary P Billman Lupeng Li Carissa K Harvest Alexia K Bryan Gabrielle R Magalski Joseph P Lopez Heather N Larson Xiao-Ming Yin Edward A Miao |
| author_facet | Taylor J Abele Zachary P Billman Lupeng Li Carissa K Harvest Alexia K Bryan Gabrielle R Magalski Joseph P Lopez Heather N Larson Xiao-Ming Yin Edward A Miao |
| author_sort | Taylor J Abele |
| collection | DOAJ |
| description | Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compared to pyroptosis in defense against an intracellular bacterial infection. We previously engineered Salmonella enterica serovar Typhimurium to persistently express flagellin, and thereby activate NLRC4 during systemic infection in mice. The resulting pyroptosis clears this flagellin-engineered strain. We now show that infection of caspase-1 or gasdermin D deficient macrophages by this flagellin-engineered S. Typhimurium induces apoptosis in vitro. Additionally, we engineered S. Typhimurium to translocate the pro-apoptotic BH3 domain of BID, which also triggers apoptosis in macrophages in vitro. During mouse infection, the apoptotic pathway successfully cleared these engineered S. Typhimurium from the intestinal niche but failed to clear the bacteria from the myeloid niche in the spleen or lymph nodes. In contrast, the pyroptotic pathway was beneficial in defense of both niches. To clear an infection, cells may have specific tasks that they must complete before they die; different modes of cell death could initiate these ‘bucket lists’ in either convergent or divergent ways. |
| first_indexed | 2024-03-09T02:19:52Z |
| format | Article |
| id | doaj.art-7eb48fcbd0d1487191217dd2ceb4740a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-09T02:19:52Z |
| publishDate | 2023-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7eb48fcbd0d1487191217dd2ceb4740a2023-12-06T17:52:14ZengeLife Sciences Publications LtdeLife2050-084X2023-12-011210.7554/eLife.89210Apoptotic signaling clears engineered Salmonella in an organ-specific mannerTaylor J Abele0https://orcid.org/0000-0002-7910-3381Zachary P Billman1Lupeng Li2Carissa K Harvest3Alexia K Bryan4Gabrielle R Magalski5Joseph P Lopez6Heather N Larson7Xiao-Ming Yin8Edward A Miao9https://orcid.org/0000-0001-7295-3490Department of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Cell Biology, Duke University School of Medicine, Durham, United StatesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Cell Biology, Duke University School of Medicine, Durham, United StatesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Biomedical Engineering, Duke University Pratt School of Engineering, Durham, United StatesDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Cell Biology, Duke University School of Medicine, Durham, United StatesDepartment of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, United StatesDepartment of Integrative Immunobiology, Duke University School of Medicine, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Cell Biology, Duke University School of Medicine, Durham, United StatesPyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compared to pyroptosis in defense against an intracellular bacterial infection. We previously engineered Salmonella enterica serovar Typhimurium to persistently express flagellin, and thereby activate NLRC4 during systemic infection in mice. The resulting pyroptosis clears this flagellin-engineered strain. We now show that infection of caspase-1 or gasdermin D deficient macrophages by this flagellin-engineered S. Typhimurium induces apoptosis in vitro. Additionally, we engineered S. Typhimurium to translocate the pro-apoptotic BH3 domain of BID, which also triggers apoptosis in macrophages in vitro. During mouse infection, the apoptotic pathway successfully cleared these engineered S. Typhimurium from the intestinal niche but failed to clear the bacteria from the myeloid niche in the spleen or lymph nodes. In contrast, the pyroptotic pathway was beneficial in defense of both niches. To clear an infection, cells may have specific tasks that they must complete before they die; different modes of cell death could initiate these ‘bucket lists’ in either convergent or divergent ways.https://elifesciences.org/articles/89210pyroptosisapoptosisSalmonellaregulated cell deathextrusion |
| spellingShingle | Taylor J Abele Zachary P Billman Lupeng Li Carissa K Harvest Alexia K Bryan Gabrielle R Magalski Joseph P Lopez Heather N Larson Xiao-Ming Yin Edward A Miao Apoptotic signaling clears engineered Salmonella in an organ-specific manner eLife pyroptosis apoptosis Salmonella regulated cell death extrusion |
| title | Apoptotic signaling clears engineered Salmonella in an organ-specific manner |
| title_full | Apoptotic signaling clears engineered Salmonella in an organ-specific manner |
| title_fullStr | Apoptotic signaling clears engineered Salmonella in an organ-specific manner |
| title_full_unstemmed | Apoptotic signaling clears engineered Salmonella in an organ-specific manner |
| title_short | Apoptotic signaling clears engineered Salmonella in an organ-specific manner |
| title_sort | apoptotic signaling clears engineered salmonella in an organ specific manner |
| topic | pyroptosis apoptosis Salmonella regulated cell death extrusion |
| url | https://elifesciences.org/articles/89210 |
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