Cytosolic Fe-superoxide dismutase safeguards Trypanosoma cruzi from macrophage-derived superoxide radical
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Significance: In Chagas disease (CD), macrophages are the first line of defense against its causative agent, Trypanosoma cruzi . Here, we show that superoxide radical (O 2 •− ), a reactive species produced during phagocytosis, diffuses toward T. cruzi , causing toxicity. Much of O 2 •− permeation involves its protonation inside the acidic phagosome. To deal with host-derived oxidants, T. cruzi contains a broad antioxidant enzyme armamentarium. Herein, we generated parasites overexpressing the cytosolic superoxide dismutase (Fe-SODB) and demonstrate that this enzyme detoxifies host-derived O 2 •− , preventing its toxicity. These parasites were more resistant to macrophage-dependent killing than the wild type and yielded higher parasitemias and parasite burden in heart tissue of infected mice, underscoring the role of Fe-SODB as a virulence factor for CD.
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The superoxide dismutase Fe-SODB in the parasitic cytosol is the main defense mechanism against antiparasitic ROS.
“The superoxide dismutase Fe-SODB in the parasitic cytosol was identified as the main defense mechanism against antiparasitic ROS.”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [283]
Toxoplasma parasites can detoxify phagosomal ROS, as demonstrated with Toxoplasma cruzii in phagosomes of J774A.1 macrophage-like cells and BMDM.
“The ability of Toxoplasma parasites to detoxify phagosomal ROS was demonstrated with the evolutionary related Toxoplasma cruzii in phagosomes of J774A.1 macrophage-like cells (J774) and BMDM [283].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [283]
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Frey, M. J., & Molinoff, P. B. (1989) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-198900145-00004 · Cited by 17 · see citing works
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Functions of ROS in Macrophages and Antimicrobial Immunity
Herb, M., & Schramm, M. (2021) · Antioxidants · doi:10.3390/antiox10020313 · Cited by 633 · see citing works
Old Dogs, New Tricks: New Insights into the Iron/Manganese Superoxide Dismutase Family
Frye, K. A., Sendra, K. M., Waldron, K. J., & Kehl-Fie, T. E. (2022) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2022.111748 · Cited by 36 · see citing works
- Authors
- Martínez, A., Prolo, C., Estrada, D., Rios, N., Alvarez, M. N., Piñeyro, M. D., Robello, C., Radi, R., & Piacenza, L.
- Affiliations
- Universidad de la República de Uruguay (UY)
- Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, 11800 Montevideo, Uruguay;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-04-12
- Volume
- 116
- Issue
- 18
- Pages
- 8879-8888
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6500117
- OpenAlex
- W2939431552
- Cited by
- 41
- References
- 101
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 15 · 2021: 5 · 2020: 6 · 2019: 1
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (1R01AI095173)
- Universidad de la República (CSIC 2014, EI 2015)
- Topics
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Keywords
- Trypanosoma cruzi, Chagas disease, cytosolic superoxide dismutase, superoxide, macrophages, phagocytosis, phagosome, antioxidant enzymes, host-pathogen interaction, virulence factors
- MeSH terms
- Animals, Cytosol, Hydrogen-Ion Concentration, Macrophages, Mice, Inbred C57BL, Oxygen Consumption, Phagosomes, Superoxides, Superoxide Dismutase, Trypanosoma cruzi, Chagas Disease, Virulence, Gene Expression Regulation, Enzymologic, Peroxynitrous Acid, Mice
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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