Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo
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The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated in gp91phox−/−, iNOS−/−, and congenic wild-type mice. Although both gp91phox−/− and iNOS−/− mice demonstrated increased susceptibility to infection with S. typhimurium compared with wild-type mice, the kinetics of bacterial replication were dramatically different in the gp91phox−/− and iNOS−/− mouse strains. Greater bacterial numbers were present in the spleens and livers of gp91phox−/− mice compared with C57BL/6 controls as early as day 1 of infection, and all of the gp91phox−/− mice succumbed to infection within 5 d. In contrast, an increased bacterial burden was detected within reticuloendothelial organs of iNOS−/− mice only beyond the first week of infection. Influx of inflammatory CD11b+ cells, granuloma formation, and serum interferon γ levels were unimpaired in iNOS−/− mice, but the iNOS-deficient granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection.
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NOX2 consists of five catalytic subunits, which assemble after phagocytosis forming an active enzymatic complex producing superoxide anions and hydrogen peroxide along with the formation of hydroxyl radicals, the latter pathway being catalyzed by iron via the Fenton reaction.
“NOX2 consists of five catalytic subunits, which assemble after phagocytosis thereby forming an active enzymatic complex producing superoxide anions and hydrogen peroxide along with the formation of hydroxyl radicals, the latter pathway being catalyzed by iron via the Fenton reaction (56, 59–61).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [61]
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 [61]
The microbicidal activity of activated macrophages depends critically on the phagocytic NADPH oxidase (NOX2/gp91phox) and the inducible form of nitric oxide synthase (iNOS/NOS2).
“The microbicidal activity of activated Mø depends critically on the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2/gp91 phox ) and the inducible form of nitric oxide (NO) synthase (iNOS/NOS2) [74,75].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [75]
During host cell-microbe interaction, macrophages can generate reactive oxygen species either via the membrane-associated NADPH oxidase complex or by the mitochondrial electron transport chain.
“During host cell-microbe interaction, macrophage can generate reactive oxygen species (ROS) either via the membrane associated NADPH oxidase complex or by the mitochondrial electron transport chain”
From Iron in immune cell function and host defense (2021) · cites this paper as [105]
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Copper Homeostasis in Salmonella Is Atypical and Copper-CueP Is a Major Periplasmic Metal Complex
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Self-citationGalectin-3 Is a Negative Regulator of Lipopolysaccharide-Mediated Inflammation
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Dynamics of bacterial growth and distribution within the liver duringSalmonellainfection
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Self-citationDevelopment of protective immunity to Salmonella, a mucosal pathogen with a systemic agenda
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Self-citationOxygen-dependent anti-Salmonella activity of macrophages
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Reactive nitrogen and oxygen species in airway inflammation
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Inhibition of bacterial DNA replication by zinc mobilization during nitrosative stress
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Self-citationVCAM-1 signals during lymphocyte migration: role of reactive oxygen species
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Self-citationA dynamic view of the spread and intracellular distribution of Salmonella enterica
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Self-citationInvasive Nontyphoidal Salmonella Disease in Africa
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Nitric Oxide and Salmonella Pathogenesis
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Reactive Nitrogen Species Contribute to Innate Host Defense againstCampylobacter jejuni
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Development of acquired immunity to Salmonella
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Self-citationSalmonella Infection in Chronic Inflammation and Gastrointestinal Cancer
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Molecular Mechanisms of Salmonella Virulence and Host Resistance
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Self-citationCellular aspects of immunity to intracellular Salmonella enterica
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Salmonella and Reactive Oxygen Species: A Love-Hate Relationship
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Self-citationPhagocytic Superoxide Specifically Damages an Extracytoplasmic Target to Inhibit or Kill Salmonella
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evasion of the NADPH phagocyte oxidase
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Self-citationThe role of iron in infections with intracellular bacteria
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Genetic susceptibility to invasive Salmonella disease
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The Salmonella SPI1 effector SopB stimulates nitric oxide production long after invasion
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- Authors
- Mastroeni, P., Vazquez-Torres, A., Fang, F. C., Xu, Y., Khan, S., Hormaeche, C. E., & Dougan, G.
- Affiliations
- University of Cambridge (GB)
- cDepartment of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
- University of Colorado Health (US)
- bDepartment of Biochemistry, Imperial College, London SW7 2AZ, United Kingdom
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2000-07-17
- Volume
- 192
- Issue
- 2
- Pages
- 237-248
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2193252
- OpenAlex
- W2102601193
- Cited by
- 399
- References
- 61
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 12 · 2023: 13 · 2022: 10 · 2021: 10 · 2020: 22 · 2019: 13 · 2018: 5 · 2017: 9 · 2016: 16 · 2015: 14 · 2014: 23 · 2013: 19 · 2012: 16
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust
- National Institutes of Health (AI39557)
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- National Institute of Allergy and Infectious Diseases (AI110181, AI 39557, R01AI039557, F32AI010181, AI44486, R01AI044486)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- inducible nitric oxide synthase, Salmonella typhimurium, salmonellosis, host resistance to infection, iNOS-deficient mice, granuloma formation, interferon-gamma, antimicrobial host defense
- MeSH terms
- NADPH Oxidase 2, Animals, Flow Cytometry, Interferon-gamma, Membrane Glycoproteins, Mice, Inbred C57BL, Salmonella Infections, Animal, Salmonella typhimurium, Nitric Oxide Synthase, NADPH Oxidases, Mice, Nitric Oxide Synthase Type II
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