Cited by 41Trypanosoma species research and implicationsRedox biology and oxidative stressResearch on Leishmaniasis Studies

Cytosolic Fe-superoxide dismutase safeguards Trypanosoma cruzi from macrophage-derived superoxide radical

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Martínez, Alejandra, Prolo, Carolina, Estrada, Damián, Rios, Natalia, Alvarez, María Noel, Piñeyro, María Dolores, Robello, Carlos, Radi, Rafael +1 more·2019·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.1821487116

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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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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
Published
2019-04-12
Volume
116
Issue
18
Pages
8879-8888
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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

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