ArticlePloS one2015
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Towards a map of the immune system manipulation network byFrontiers in cellular and infection microbiology · 2025Review
- Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1.Journal of extracellular vesicles · 2024Article
- Pirfenidone Prevents Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy.International journal of molecular sciences · 2024Article
- Article
- Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?Frontiers in immunology · 2022Review
- piRNAs as Modulators of Disease Pathogenesis.International journal of molecular sciences · 2021Review
- Host-parasite dynamics in Chagas disease from systemic to hyper-local scales.Parasite immunology · 2021Review
- Article
- The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics.Frontiers in cellular and infection microbiology · 2021Review
- All Roads Lead to Cytosol:Frontiers in cellular and infection microbiology · 2021Review
- Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Differential Role of TGF-β in Extracellular Matrix Regulation DuringInternational journal of molecular sciences · 2019Article
- Cardiac Chagas Disease: MMPs, TIMPs, Galectins, and TGF-Disease markers · 2019Review
- Catalytic Mechanism of Cruzain from Trypanosoma cruzi As Determined from Solvent Kinetic Isotope Effects of Steady-State and Pre-Steady-State Kinetics.Biochemistry · 2018Article
- A Brief View of the Surface Membrane Proteins fromJournal of parasitology research · 2017Review
- Interactions between Trypanosoma cruzi Secreted Proteins and Host Cell Signaling Pathways.Frontiers in microbiology · 2016Review
- Mechanisms of Infectivity and Evasion Derived from Microvesicles Cargo Produced byFrontiers in cellular and infection microbiology · 2016Review
- Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion process of mammalian host cells is described to be dependent on the activation of the host TGF-β signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be an important activator of latent TGF-β and thereby trigger TGF-β-mediated events crucial for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite lysates and purified cruzipain were able to activate latent TGF-β in vitro. This activation could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented latent TGF-β activation. We also observed that T. cruzi invasion, as well as parasite intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-β neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be completely inhibited by addition of a neutralizing anti-TGF-β antibody. Taken together, these results demonstrate that the activities of cruzipain and TGF-β in the process of cell invasion are functionally linked. Our data suggest that cruzipain inhibition is an interesting chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity, but also due to the inhibitory effect on TGF-β activation.
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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.