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Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens
Open accessAbstract
This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity. Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant, and yet also mutually redundant, in host defense. In combination, the contribution of these two enzymes appears to be greater than previously appreciated. The remainder of this review focuses on a relatively new field, the basis of microbial resistance to RNI. Experimental tuberculosis provides an important example of an extended, dynamic balance between host and pathogen in which RNI play a major role. In diseases such as tuberculosis, a molecular understanding of host–pathogen interactions requires characterization of the defenses used by microbes against RNI, analogous to our understanding of defenses against reactive oxygen intermediates. Genetic and biochemical approaches have identified candidates for RNI-resistance genes in Mycobacterium tuberculosis and other pathogens.
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“In addition, NO causes the formation of reactive nitrogen species (such as peroxynitrite) which can damage mitochondrial function and which have been shown to have strong antifungal activity (26).”
From Inhibition of Classical and Alternative Modes of Respiration in Candida albicans Leads to Cell Wall Remodeling and Increased Macrophage Recognition (2019) · cites this paper as [26]
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In the citing paper
“iNOS catalyzed high output formation of the labile radical NO by macrophages (Nathan and Shiloh, 2000; Bogdan, 2001) which exerts direct anti-microbial effector functions.”
From Iron at the interface of immunity and infection (2014) · cites this paper as Nathan and Shiloh, 2000
In the citing paper
“Using arginine and oxygen, the homodimeric NOS2 generates NO and citrulline, as one subunit transfers electrons between NADPH, FAD, flavin mononucleotide to the heme iron of the second subunit (56, 57).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [56]
In the citing paper
“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 [56]
In the citing paper
“Both NOX2/gp91 phox and iNOS/ NOS2 are prototypical hemoproteins that use Fe-heme to catalyze the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), respectively [76].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [76]
In the citing paper
“Moreover, extracellular hemoglobin may also exert protective effects based on NO and ONNO À detoxification [76,80,197].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [76]
In the citing paper
“For example, generation of nitric oxide (NO•) by the inducible nitric oxide synthase (iNOS/NOS2) is a well established host defense mechanism that confers resistance to Salmonella, Leishmania or Mycobacteria (62).”
From Innate Nutritional Immunity (2018) · cites this paper as [62]
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Cites
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Metadata
- Authors
- Nathan, C., & Shiloh, M. U.
- Affiliations
- Cornell University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-08
- Volume
- 97
- Issue
- 16
- Pages
- 8841-8848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC34021
- OpenAlex
- W2113120391
- Cited by
- 1,469
- References
- 105
- Citations by year
- 2026: 26 · 2025: 29 · 2024: 42 · 2023: 32 · 2022: 49 · 2021: 42 · 2020: 59 · 2019: 51 · 2018: 56 · 2017: 62 · 2016: 66 · 2015: 64 · 2014: 72 · 2013: 70 · 2012: 81
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- reactive oxygen species, reactive nitrogen intermediates, host-pathogen interaction, inducible nitric oxide synthase, NADPH oxidase, inducible nitric oxide, Mycobacterium tuberculosis, tuberculosis, knockout mice, innate immunity
- MeSH terms
- Animals, Humans, Mammals, Mycobacterium tuberculosis, Nitrogen, Reactive Oxygen Species, Nitric Oxide Synthase, NADPH Oxidases, Mice
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