Differential cytokine profiling in Chagasic patients according to their arrhythmogenic-status

Rodríguez-Angulo, Héctor O.; Márques, Juan; Mendoza, Iván; Villegas, Marco A.; Mijares, Alfrédo; Gironès, Núria; Fresno, Manuel

doi:10.1186/s12879-017-2324-x

Cited by 23 publications

(23 citation statements)

References 38 publications

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“…The consequence of myofibroblast differentiation is the increased expression and deposition of ECM proteins that further contribute to the fibrotic process [ 16 ]. Inflammation and fibrosis are hallmarks of CCC [ 6 , 34 – 36 ], with production of cytokines that contribute to pathogenesis [ 37 ] and co-localization of T. cruzi DNA or antigens with inflammatory infiltrate and fibrosis in cardiac tissue was also observed [ 6 , 7 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi activates mouse cardiac fibroblasts in vitro leading to fibroblast-myofibroblast transition and increase in expression of extracellular matrix proteins

Coelho

Pereira

et al. 2018

Parasites Vectors

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BackgroundCardiac fibrosis is a consequence of chronic chagasic cardiomyopathy (CCC). In other cardiovascular diseases, the protagonist role of fibroblasts in cardiac fibrosis is well established. However, the role of cardiac fibroblasts (CFs) in fibrosis during the CCC is not clear. Here, our aim was to investigate the effect of Trypanosoma cruzi, the etiological agent of Chagas disease on CFs activation.MethodsCardiac fibroblasts were purified from primary cultures of mouse embryo cardiac cells. After two passages, cells were infected with T. cruzi (Y strain) and analyzed at different times for determination of infectivity, activation and production of extracellular matrix components (fibronectin, laminin and collagen IV) by immunofluorescence and western blot.ResultsAt second passage, cultures were enriched in CFs (95% of fibroblasts and 5% of cardiomyocytes), as revealed by presence of alpha-smooth muscle actin (α-SMA) and discoidin domain receptor 2 (DDR2) and absence of sarcomeric tropomyosin (ST) protein expression. Trypanosoma cruzi infection induced fibroblast-myofibroblast transition, with increased expression of α-SMA after 6 and 24 h post-infection (hpi). Fibronectin was increased at 6, 24 and 48 hpi, laminin was increased at 6 and 24 hpi and collagen IV was increased at 6 hpi.ConclusionsOur results showed that T. cruzi activates CFs, inducing activation and exacerbates ECM production. Furthermore, our data raise the possibility of the involvement of CFs in heart fibrosis during Chagas disease.

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Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi activates mouse cardiac fibroblasts in vitro leading to fibroblast-myofibroblast transition and increase in expression of extracellular matrix proteins

Coelho

Pereira

et al. 2018

Parasites Vectors

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“…The complexity of Th1 and Th17 responses to T. cruzi infection is highlighted by the observation that selective downregulation of Th1 cells and Th17 cells by parasite trans-sialidases or the expression of other immunomodulatory factors promotes both host survival and low-level parasite persistence by reducing both protective and harmful effects (113,116). Levels of IFN-γ, IL-2, and IL-10 may predict the risks of arrhythmia and sudden death in Chagas patients, with elevated IL-2 most strongly correlated with a high risk of death (117). However, the frequency of activated T cells is inversely related to disease severity, and chronic infection may lead to clonal exhaustion and reduced numbers of memory T cells (118)(119)(120)(121).…”

Section: Adaptive Immunity To T Cruzi Infectionmentioning

confidence: 99%

Pathology and Pathogenesis of Chagas Heart Disease

Bonney

Luthringer

Kim

et al. 2019

Annu. Rev. Pathol. Mech. Dis.

190

201

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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 this wealth of knowledge, it is still impossible to predict what will happen in an individual infected with T. cruzi because of the tremendous variability in clonal parasite virulence and human susceptibility to infection and the lack of definitive molecular predictors of outcome from either side of the host–parasite equation. Further, while several distinct mechanisms of pathogenesis have been studied in isolation, it is certain that multiple coincident mechanisms combine to determine the ultimate outcome. For these reasons, Chagas disease is best considered a collection of related but distinct illnesses. This review highlights the pathology and pathogenesis of the most common adverse sequela of T. cruzi infection—Chagas heart disease—and concludes with a discussion of key unanswered questions and a view to the future.

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“…In addition, IL-22, a pleiotropic cytokine mainly produced by T H 17 cells, is secreted in response to T. cruzi infection in mice, in an IL-23-dependent fashion, which seems to contribute to the regulation of inflammatory cytokines ( 198 ). With regards to human patients, the panorama is less clear: while some authors have shown that a higher frequency of IL-17 + cells within the CD3 + CD4 + subset of PBMC is associated with milder forms of the disease ( 99 , 199 ), and a correlation of IL-17A plasma levels with better cardiac function ( 200 ), others found increased levels of IL-17 in the sera of patients with higher risk of sudden death ( 201 ). However, it should be kept in mind that, as it was discussed above, T H 17 are not the only cell lineage producing IL-17 in response to T. cruzi .…”

Section: Adaptive Immunitymentioning

confidence: 99%

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

2018

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Trypanosoma cruzi interacts with the different arms of the innate and adaptive host's immune response in a very complex and flowery manner. The history of host-parasite co-evolution has provided this protozoan with means of resisting, escaping or subverting the mechanisms of immunity and establishing a chronic infection. Despite many decades of research on the subject, the infection remains incurable, and the factors that steer chronic Chagas disease from an asymptomatic state to clinical onset are still unclear. As the relationship between T. cruzi and the host immune system is intricate, so is the amount and diversity of scientific knowledge on the matter. Many of the mechanisms of immunity are fairly well understood, but unveiling the factors that lead each of these to success or failure, within the coordinated response as a whole, requires further research. The intention behind this Review is to compile the available information on the different aspects of the immune response, with an emphasis on those phenomena that have been studied and confirmed in the human host. For ease of comprehension, it has been subdivided in sections that cover the main humoral and cell-mediated components involved therein. However, we also intend to underline that these elements are not independent, but function intimately and concertedly. Here, we summarize years of investigation carried out to unravel the puzzling interplay between the host and the parasite.

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Differential cytokine profiling in Chagasic patients according to their arrhythmogenic-status

Cited by 23 publications

References 38 publications

Trypanosoma cruzi activates mouse cardiac fibroblasts in vitro leading to fibroblast-myofibroblast transition and increase in expression of extracellular matrix proteins

Trypanosoma cruzi activates mouse cardiac fibroblasts in vitro leading to fibroblast-myofibroblast transition and increase in expression of extracellular matrix proteins

Pathology and Pathogenesis of Chagas Heart Disease

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

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