Disparate Impact of Oxidative Host Defenses Determines the Fate of Salmonella during Systemic Infection in Mice
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Reactive oxygen and nitrogen species function in host defense via mechanisms that remain controversial. Pathogens might encounter varying levels of these species, but bulk measurements cannot resolve such heterogeneity. We used single-cell approaches to determine the impact of oxidative and nitrosative stresses on individual Salmonella during early infection in mouse spleen. Salmonella encounter and respond to both stresses, but the levels and impact vary widely. Neutrophils and inflammatory monocytes kill Salmonella by generating overwhelming oxidative stress through NADPH oxidase and myeloperoxidase. This controls Salmonella within inflammatory lesions but does not prevent their spread to more permissive resident red pulp macrophages, which generate only sublethal oxidative bursts. Regional host expression of inducible nitric oxide synthase exposes some Salmonella to nitrosative stress, triggering effective local Salmonella detoxification through nitric oxide denitrosylase. Thus, reactive oxygen and nitrogen species influence dramatically different outcomes of disparate Salmonella-host cell encounters, which together determine overall disease progression.
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Recent evidence obtained in models of S. typhimurium infection indicates specific compartmentalization of nitrosative and oxidative stress in macrophages and thus divergent effects on the fate and propagation of bacteria.
“Of interest, recent evidence obtained in models of S. typhiumrium infection indicate specific compartmentalization of nitrosative and oxidative stress in macrophages and thus divergent effects on the fate and propagation of bacteria, extending previous work on cycle specific susceptibility of these bacteria to either of these stress responses (61, 68, 69).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [69]
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- Authors
- Burton, N. A., Schürmann, N., Casse, O., Steeb, A. K., Claudi, B., Zankl, J., Schmidt, A., & Bumann, D.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Bumann, Dirk
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 15
- Issue
- 1
- Pages
- 72-83
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2034408518
- Cited by
- 175
- References
- 77
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 13 · 2023: 9 · 2022: 11 · 2021: 15 · 2020: 17 · 2019: 17 · 2018: 9 · 2017: 19 · 2016: 15 · 2015: 19 · 2014: 10
- FWCI
- 9.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SPP 1316)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Keywords
- Salmonella, reactive oxygen species, reactive nitrogen species, oxidative stress, nitrosative stress, host-pathogen interaction, neutrophils, inflammatory monocytes, NADPH oxidase, myeloperoxidase, red pulp macrophages, inducible nitric oxide synthase, single-cell tracking, systemic infection, spleen, mouse model
- MeSH terms
- Animals, Female, Macrophages, Monocytes, Peroxidase, Neutrophils, Oxygenases, Salmonella Infections, Salmonella typhimurium, Spleen, Gene Expression, Respiratory Burst, Reactive Oxygen Species, NADPH Oxidases, Reactive Nitrogen Species, Mice, Nitric Oxide Synthase Type II, Host-Pathogen Interactions, Single-Cell Analysis
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