Apoptotic signaling clears engineered Salmonella in an organ-specific manner.

Autor:	Abele TJ; Department 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., Billman ZP; Department 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 States., Li L; Department 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., Harvest CK; Department 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 States., Bryan AK; Department of Integrative Immunobiology, Duke University School of Medicine, Durham, United States.; Department of Biomedical Engineering, Duke University Pratt School of Engineering, Durham, United States., Magalski GR; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United States., Lopez JP; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United States., Larson HN; Department 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., Yin XM; Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, United States., Miao EA; Department 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.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Dec 06; Vol. 12. Date of Electronic Publication: 2023 Dec 06.
DOI:	10.7554/eLife.89210
Abstrakt:	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. Competing Interests: TA, ZB, LL, CH, AB, GM, JL, HL, XY, EM No competing interests declared (© 2023, Abele et al.)
Databáze:	MEDLINE
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