ArticleInfection and immunity2002
Increased Trypanosoma cruzi invasion and heart fibrosis associated with high transforming growth factor beta levels in mice deficient in alpha(2)-macroglobulin.
Article in Infection and immunity, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease.Biomolecules · 2022Review
- Signal Transducer and Activator of Transcription-3 Modulation of Cardiac Pathology in Chronic Chagasic Cardiomyopathy.Frontiers in cellular and infection microbiology · 2021Article
- Alpha-2-Macroglobulin in Inflammation, Immunity and Infections.Frontiers in immunology · 2021Review
- Interleukin-9 in Immunopathology ofFrontiers in cellular and infection microbiology · 2021Article
- 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
- Deletion of Pregnancy Zone Protein and Murinoglobulin-1 Restricts the Pathogenesis of West Nile Virus Infection in Mice.Frontiers in microbiology · 2019Article
- Trypanosoma cruzi High Mobility Group B (TcHMGB) can act as an inflammatory mediator on mammalian cells.PLoS neglected tropical diseases · 2017Article
- Role of Inactive and ActiveFrontiers in microbiology · 2017Article
- Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection.Cellular microbiology · 2014Article
- Together and apart: inhibition of DNA synthesis by connexin-43 and its relationship to transforming growth factor β.Frontiers in pharmacology · 2013Article
- A phosphoproteomic approach towards the understanding of the role of TGF-β in Trypanosoma cruzi biology.PloS one · 2012Article
- Oral administration of GW788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in Chagas disease.PLoS neglected tropical diseases · 2012Article
- Specific antibodies induce apoptosis in Trypanosoma cruzi epimastigotes.Parasitology research · 2010Article
- Pharmacological inhibition of transforming growth factor beta signaling decreases infection and prevents heart damage in acute Chagas' disease.Antimicrobial agents and chemotherapy · 2009Article
- The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome.Proteome science · 2009Article
- Regulation of monocytes and macrophages cell fate.Frontiers in bioscience (Landmark edition) · 2009Review
- Molecular dissection of the human alpha2-macroglobulin subunit reveals domains with antagonistic activities in cell signaling.The Journal of biological chemistry · 2008Article
- SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion.Antimicrobial agents and chemotherapy · 2007Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosoma cruzi proteinases are involved in host cell invasion in human patients and in mouse models. In mice, murine alpha(2)-macroglobulin (MAM) and murinoglobulin are circulating plasma proteinase inhibitors that also have important roles in inflammation and immune modulation. To define their role in experimental Chagas disease, we investigated the susceptibility to T. cruzi infection of mice that are deficient only in alpha2-macroglobulins (AM-KO) or in both MAM and monomeric murinoglobulin-1 (MM-KO), relative to the wild type (WT). Despite the high parasite load, parasitemia was lower in AM-KO and MM-KO mice than in WT mice. Nevertheless, we observed a significantly higher parasite load in the hearts of AM-KO and MM-KO mice, i.e., more amastigote nests and inflammatory infiltrates than in WT mice. This result demonstrates a protective role for MAM in the acute phase of murine T. cruzi infection. We further demonstrated in vitro that human alpha2-macroglobulins altered the trypomastigote morphology and motility in a dose-dependent way, and that also impaired T. cruzi invasion in cardiomyocytes. Finally, we demonstrated that the levels of transforming growth factor beta in AM-KO mice increased significantly in the third week postinfection, concomitant with high amastigote burden and important fibrosis. Combined, these in vivo and in vitro findings demonstrate that the MAM contribute to the resistance of mice to acute myocarditis induced by experimental T. cruzi infection.
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