Betulinic Acid Derivative BA5, Attenuates Inflammation and Fibrosis in Experimental Chronic Chagas Disease Cardiomyopathy by Inducing IL-10 and M2 Polarization

In conclusion, BA5 had a potent anti-inflammatory activity on a model of parasite-driven heart disease related to IL-10 production and a switch from M1 to M2 subset of macrophages.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

by Roberto Rodrigues Ferreira, Rayane da Silva Abreu, Glaucia Vilar-Pereira, Wim Degrave, Marcelo Meuser-Batista, Nilma Val éria Caldeira Ferreira, Otacílio da Cruz Moreira, Natália Lins da Silva Gomes, Elen Mello de Souza, Isalira P. Ramos, Sabine Bailly, Jean-Jacques Feige, Joseli Lannes-Vieira, Tania C. de Araújo-Jorge, Mariana Caldas Waghabi TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated. The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expre...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract The infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease, a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, culminating in heart failure and high rates of sudden death. CCC pathogenesis is influenced by both host and parasite factors and is proposed to be mostly immune-driven. Chemokines are crucial players in orchestrating immune cell recruitment to infected tissues and inflammation. Herein, we...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research
Conclusions: We suggest some distinct molecular mechanisms for production of IL-1β in innate immune cells from patients with different clinical forms of Chagas disease. MMP-2 and MMP-9 gelatinases are associated with distinct disease outcomes and IL-1β production. Introduction Chagas disease, also known as American trypanosomiasis, is a neglected parasitic disease caused by the protozoan Trypanosoma cruzi (1), that affects millions of people in the world (2). During the acute phase, a diffuse and intense inflammation in the cardiomyocytes is observed, which is composed mainly of neutrophils, monocytes, and ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite Trypanosoma cruzi. One way T. cruzi is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. The epidemiology of T. cruzi and Chagas heart disease and the varied mechanisms leading to myocyte destruction, mononuclear cell infiltration, fibrosis, and edema in the heart have been extensively studied by hundreds of scientists for more than 100 years. Despite...
Source: Annual Review of Pathology - Category: Pathology Authors: Tags: Annu Rev Pathol Source Type: research
AbstractChagas disease is caused by a parasite infection endemic of the Americas. Traditionally observed in rural areas of Latin America, current migration trends have turned Chagas disease into a global epidemic. Acute infection is rarely severe and once it resolves, some patients can develop cardiomyopathy as part of the chronic form many years later. Multiple factors related with both the host and the parasite determine the susceptibility and progression to cardiomyopathy. Current imaging techniques are able to identify cardiac autonomic denervation, perfusion abnormalities, and myocardial fibrosis at an early of stage ...
Source: Journal of Nuclear Cardiology - Category: Nuclear Medicine Source Type: research
CONCLUSIONS: Our data suggest no significant contribution of the analysed gene variants of cytokine-related molecules to development/severity of Chagas' heart disease, reinforcing the idea that parasite/host interplay is critical to CD outcomes. PMID: 29768622 [PubMed - in process]
Source: Memorias do Instituto Oswaldo Cruz - Category: Infectious Diseases Authors: Tags: Mem Inst Oswaldo Cruz Source Type: research
Chagas disease, caused by infection with the protozoan parasite Trypanosoma cruzi, is a leading cause of heart disease ("chagasic cardiomyopathy") in Latin America, disproportionately affecting people in resource-poor areas. The efficacy of currently approved pharmaceutical treatments is limited mainly to acute infection, and there are no effective treatments for the chronic phase of the disease. Preclinical models of Chagas disease have demonstrated that antigen-specific CD8+ gamma interferon (IFN-)-positive T-cell responses are essential for reducing parasite burdens, increasing survival, and decreasing cardiac...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Fungal and Parasitic Infections Source Type: research
The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi–specific D...
Source: The Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: PATHOGENESIS AND HOST RESPONSE Source Type: research
Conclusion : Our current study shows a putative mechanism of action of Cur involving inhibition of the Ca2+/NFAT-dependent, pathogenic COX-2/mPGES-1/PGE2 pathway in T. cruzi-infected myocytes, underlying cardioprotection achieved in Cur-treated infected mice. With a view to the limited therapeutic possibilities available, Cur represents a promising approach for the treatment of Chagas heart disease. Graphical abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
Summary Host and parasite diversity are suspected to be key factors in Chagas disease pathogenesis. Experimental investigation of underlying mechanisms is hampered by a lack of tools to detect scarce, pleiotropic infection foci. We developed sensitive imaging models to track Trypanosoma cruzi infection dynamics and quantify tissue‐specific parasite loads, with minimal sampling bias. We used this technology to investigate cardiomyopathy caused by highly divergent parasite strains in BALB/c, C3H/HeN and C57BL/6 mice. The gastrointestinal tract was unexpectedly found to be the primary site of chronic infection in all models...
Source: Cellular Microbiology - Category: Microbiology Authors: Tags: Research article Source Type: research
More News: Allergy & Immunology | Cardiology | Cardiomyopathy | Chagas Disease | Genetics | Heart | Heart Disease | Parasitic Diseases | Parasitology | Sports Medicine