Antimicrobial reactive oxygen and nitrogen species: concepts and controversies
Abstract
Phagocyte-derived reactive oxygen and nitrogen species are of crucial importance for host resistance to microbial pathogens. Decades of research have provided a detailed understanding of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection. However, differences of opinion remain with regard to their host specificity, cell biology, sources and interactions with one another or with myeloperoxidase and granule proteases. More than a century after Metchnikoff first described phagocytosis, and more than four decades after the discovery of the burst of oxygen consumption that is associated with microbial killing, the seemingly elementary question of how phagocytes inhibit, kill and degrade microorganisms remains controversial. This review updates the reader on these concepts and the topical questions in the field.
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After crossing the phagosomal membrane, NO and ROI can spontaneously react in the phagosomal lumen to generate nitrogen dioxide, peroxynitrite, dinitrogen trioxide, nitrosothiols, nitroxyl, and dinitrosyl-iron complexes.
“After crossing the phagosomal membrane, NO and ROI can spontaneously react in the phagosomal lumen to generate nitrogen dioxide (NO2), peroxynitrite (ONOO−), dinitrogen trioxide (N2O3), nitrosothiols, nitroxyl (HNO), and dinitrosyl-iron complexes (58).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [58]
Activated macrophages produce reactive oxygen intermediates via activation of NOX2.
“In parallel, activated macrophages produce reactive oxygen intermediates (ROI) via activation of NOX2 (58).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [58]
Highly reactive intermediates execute their microbicidal activity by oxidative destruction of membrane lipids, DNA, thiol and tyrosine residues, whereas NO can exert toxicity by directly targeting iron sulfur clusters of central metabolic enzymes.
“Nonetheless, these highly reactive intermediates execute their microbicidal activity by oxidative destruction of membrane lipids, DNA, thiol and tyrosine residues, whereas NO can exert toxicity by directly targeting iron sulfur cluster of central metabolic enzymes (57, 58, 70–72).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [58]
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- Authors
- Fang, F. C.
- Affiliations
- University of Washington (US)
- Corresponding author
- Fang, Ferric C.
- ORCID
- Fang, Ferric C.
- Venue
- Nature Reviews Microbiology
- Published
- 2004-10
- Volume
- 2
- Issue
- 10
- Pages
- 820-832
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- OpenAlex
- W2066515050
- Cited by
- 1,676
- References
- 245
- Citations by year
- 2026: 56 · 2025: 73 · 2024: 81 · 2023: 72 · 2022: 89 · 2021: 129 · 2020: 104 · 2019: 113 · 2018: 83 · 2017: 88 · 2016: 110 · 2015: 70 · 2014: 93 · 2013: 79 · 2012: 90
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- 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
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- reactive oxygen species, reactive nitrogen species, phagocytes, antimicrobial host defense, phagocytosis, myeloperoxidase, microbial killing, host specificity, respiratory burst
- MeSH terms
- Granulomatous Disease, Chronic, Humans, Immunity, Innate, Phagocytes, Polymorphism, Genetic, Cytokines, Reactive Oxygen Species, Nitric Oxide Synthase, Reactive Nitrogen Species, Nitric Oxide Synthase Type II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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