ArticleThe Journal of clinical investigation2012
Oxidative stress fuels Trypanosoma cruzi infection in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review.Parasitology · 2020Pooled it
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- Metformin improves CD8+ T cell responses and parasitemia control via macrophage modulation during Trypanosoma cruzi infection.Journal of leukocyte biology · 2025Article
- Translesion synthesis and microhomology-mediated end-joining repair in trypanosomatids.PLoS neglected tropical diseases · 2025Review
- Energy metabolism inmBio · 2025Review
- Upregulation of Nrf2 attenuates Angiostrongylus cantonensis-induced parasitic meningitis in mice.Parasites & vectors · 2025Article
- Exploring the Mechanisms of Iron Overload-Induced Liver Injury in Rats Based on Transcriptomics and Proteomics.Biology · 2025Article
- Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection.PLoS pathogens · 2025Article
- Synthesis and Biological Evaluation of New Chalcogen Semicarbazone (Journal of medicinal chemistry · 2024Article
- Heart function enhancement by an Nrf2-activating antioxidant in acute Y-strain Chagas disease, but not in chronic Colombian or Y-strain.PLoS neglected tropical diseases · 2024Article
- Review
- Neutrophils versus Protozoan Parasites:Microorganisms · 2024Review
- AnHeliyon · 2024Article
- Review
- ROS are required for the germinative cell proliferation and metacestode larval growth ofFrontiers in microbiology · 2024Article
- Metacyclogenesis as the Starting Point of Chagas Disease.International journal of molecular sciences · 2023Review
- Access and utilization of host-derived iron by Leishmania parasites.Journal of biochemistry · 2023Review
- Genetic modification of miR-34a enhances efficacy of transplanted human dental pulp stem cells after ischemic stroke.Neural regeneration research · 2023Article
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Iron Uptake ControlsAntioxidants (Basel, Switzerland) · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative damage contributes to microbe elimination during macrophage respiratory burst. Nuclear factor, erythroid-derived 2, like 2 (NRF2) orchestrates antioxidant defenses, including the expression of heme-oxygenase-1 (HO-1). Unexpectedly, the activation of NRF2 and HO-1 reduces infection by a number of pathogens, although the mechanism responsible for this effect is largely unknown. We studied Trypanosoma cruzi infection in mice in which NRF2/HO-1 was induced with cobalt protoporphyrin (CoPP). CoPP reduced parasitemia and tissue parasitism, while an inhibitor of HO-1 activity increased T. cruzi parasitemia in blood. CoPP-induced effects did not depend on the adaptive immunity, nor were parasites directly targeted. We also found that CoPP reduced macrophage parasitism, which depended on NRF2 expression but not on classical mechanisms such as apoptosis of infected cells, induction of type I IFN, or NO. We found that exogenous expression of NRF2 or HO-1 also reduced macrophage parasitism. Several antioxidants, including NRF2 activators, reduced macrophage parasite burden, while pro-oxidants promoted it. Reducing the intracellular labile iron pool decreased parasitism, and antioxidants increased the expression of ferritin and ferroportin in infected macrophages. Ferrous sulfate reversed the CoPP-induced decrease in macrophage parasite burden and, given in vivo, reversed their protective effects. Our results indicate that oxidative stress contributes to parasite persistence in host tissues and open a new avenue for the development of anti-T. cruzi drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.