ArticleThe Journal of biological chemistry2011
Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: consequences for oxidative killing and role of microbial peroxiredoxins in infectivity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 215 citations in OpenAlex.
- Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review.Parasitology · 2020Pooled it
- Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection.Immunology · 2018Trial
- Nitration in cancer signaling.Redox biology · 2026Review
- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Synergistic effects of oxidative and acid stress on bacterial membranes of Escherichia coli and Staphylococcus simulans.Communications biology · 2024Article
- Emerging insights into macrophage extracellular traps in bacterial infections.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- The End Justifies the Means: Chagas Disease from a Perspective of the Host-Life (Basel, Switzerland) · 2024Review
- New insights intoFrontiers in immunology · 2024Review
- Metacyclogenesis as the Starting Point of Chagas Disease.International journal of molecular sciences · 2023Review
- Holothurian triterpene glycoside cucumarioside ACancer cell international · 2023Article
- From Benznidazole to New Drugs: Nanotechnology Contribution in Chagas Disease.International journal of molecular sciences · 2023Review
- Identification and quantification of protein nitration sites in human coronary artery smooth muscle cells in the absence and presence of peroxynitrous acid/peroxynitrite.Redox biology · 2023Article
- Article
- Immunopathological Mechanisms Underlying Cardiac Damage in Chagas Disease.Pathogens (Basel, Switzerland) · 2023Review
- The roles of COX-2 in protozoan infection.Frontiers in immunology · 2023Review
- Consumption of Galactose byPathogens (Basel, Switzerland) · 2022Article
- Interplay of carbon dioxide and peroxide metabolism in mammalian cells.The Journal of biological chemistry · 2022Review
- Crystal structure of Trypanosoma cruzi heme peroxidase and characterization of its substrate specificity and compound I intermediate.The Journal of biological chemistry · 2022Article
- IFN-induced cell-autonomous immune mechanisms in the control of intracellular protozoa.Parasitology research · 2022Review
- Mitochondrial CaAntioxidants & redox signaling · 2022Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Macrophage-derived radicals generated by the NADPH oxidase complex and inducible nitric-oxide synthase (iNOS) participate in cytotoxic mechanisms against microorganisms. Nitric oxide ((•)NO) plays a central role in the control of acute infection by Trypanosoma cruzi, the causative agent of Chagas disease, and we have proposed that much of its action relies on macrophage-derived peroxynitrite (ONOO(-) + ONOOH) formation, a strong oxidant arising from the reaction of (•)NO with superoxide radical (O(2)(-)). Herein, we have shown that internalization of T. cruzi trypomastigotes by macrophages triggers the assembly of the NADPH oxidase complex to yield O(2)(-) during a 60-90-min period. This does not interfere with IFN-γ-dependent iNOS induction and a sustained (•)NO production (∼24 h). The major mechanism for infection control via reactive species formation occurred when (•)NO and O(2)() were produced simultaneously, generating intraphagosomal peroxynitrite levels compatible with microbial killing. Moreover, biochemical and ultrastructural analysis confirmed cellular oxidative damage and morphological disruption in internalized parasites. Overexpression of cytosolic tryparedoxin peroxidase in T. cruzi neutralized macrophage-derived peroxynitrite-dependent cytotoxicity to parasites and favored the infection in an animal model. Collectively, the data provide, for the first time, direct support for the action of peroxynitrite as an intraphagosomal cytotoxin against pathogens and the premise that microbial peroxiredoxins facilitate infectivity via decomposition of macrophage-derived peroxynitrite.
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What OpenQuestion holds
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.