Fifteen Years after the Definition of Trypanosoma cruzi DTUs: What Have We Learned?

Zingales, Bianca; Macedo, Andréa M.

doi:10.3390/life13122339

Cited by 15 publications

(6 citation statements)

References 185 publications

(288 reference statements)

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“…encompassing a broad spectrum of genotypes and phenotypes. 14,15 However, the precise nature of this relationship remains incompletely understood. The surface of T. cruzi is rich in pathogen-associated molecular patterns, 16 while host tissue injury releases damage-associated molecular patterns.…”

Section: Immunologic Remodeling In Ccmmentioning

confidence: 99%

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

Roman-Campos,

Marin-Neto,

Santos-Miranda

et al. 2024

Circulation Research

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Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

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Section: Immunologic Remodeling In Ccmmentioning

confidence: 99%

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

Roman-Campos,

Marin-Neto,

Santos-Miranda

et al. 2024

Circulation Research

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“…Heart transplantation is a therapeutic option for those patients with advanced heart failure refractory to medical therapy. Reactivation of Chagas disease is a common finding under immunosuppressive conditions, such as AIDS, autoimmune diseases, cancer (and the chemotherapy used to treat it), and, obviously, pharmacological immunosuppression to avoid allograph rejection ( 250 – 252 ).…”

Section: Immunosuppression and Reactivation Of The Chagas Diseasementioning

confidence: 99%

“…It is well established that a high immunossupression is able to modify the cytokine profile of type I T helper lymphocytes to Th2-type response. This environment constitutes a favorable condition for exacerbation of the disease and its symptoms including fever, anorexia, myalgia, diarrhea, panniculitis, myocarditis, meningoencephalitis, and encephalitis ( 252 ). In this context, some T. cruzi DTUs seem to contribute to increase the risk of certain morbidities in comparison to others.…”

Section: Immunosuppression and Reactivation Of The Chagas Diseasementioning

confidence: 99%

“…In this context, some T. cruzi DTUs seem to contribute to increase the risk of certain morbidities in comparison to others. On the other hand, since host–pathogen interactions are complex, with several unknown aspects influencing the fate of infections, the interplay between the pathogen and the host’s immune response must be critical in determining disease evolution ( 252 ). The alignment between the distribution of T. cruzi DTUs and disease severity has led to a general association of TcI with oral transmission and severe acute cases in the North and Central Americas and the Amazon region in Brazil; TcIII and TcIV associated with oral transmission and acute cases in the Amazon region in Brazil and Venezuela, respectively ( 252 ).…”

Section: Immunosuppression and Reactivation Of The Chagas Diseasementioning

confidence: 99%

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New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes

Silvestrini,

Alessio,

Frias

et al. 2024

Front. Immunol.

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Chagas disease, caused by Trypanosoma cruzi, remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called “discrete typing units” (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of T. cruzi species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how T. cruzi genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of T. cruzi, evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary T. cruzi DTU. An important aspect observed in previous studies is that the genetic variability of T. cruzi can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that T. cruzi DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease’s pathogenesis. Several teams have investigated the correlation between T. cruzi DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the T. cruzi infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of T. cruzi and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with T. cruzi.

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“…While there has been extensive research in the molecular epidemiology field of T. cruzi , studies exploring the impact of genetic diversity on transmission cycles, geographic distribution, and clinical manifestations of CD are scarce, and conclusive associations have not been firmly established (Jiménez et al 2019 ; Messenger et al 2015 ; Zingales 2018 ; Zingales et al 2009 ). Nevertheless, the exploration of genetic diversity has provided valuable insights into the intricate interplay between host and pathogen and the genetic factors that influence the evolution of the disease (Zingales & Macedo 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of metacyclogenesis and infection curves in different discrete typing units of Trypanosoma cruzi

Cáceres,

Cruz-Saavedra,

Patiño

et al. 2024

Parasitol Res

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Chagas disease (CD), caused by the complex life cycle parasite Trypanosoma cruzi, is a global health concern and impacts millions globally. T. cruzi’s genetic variability is categorized into discrete typing units (DTUs). Despite their widespread presence in the Americas, a comprehensive understanding of their impact on CD is lacking. This study aims to analyze life cycle traits across life cycle stages, unraveling DTU dynamics. Metacyclogenesis curves were generated, inducing nutritional stress in epimastigotes of five DTUs (TcI (MG), TcI (DA), TcII(Y), TcIII, TcIV, and TcVI), resulting in metacyclic trypomastigotes. Infection dynamics in Vero cells from various DTUs were evaluated, exploring factors like amastigotes per cell, cell-derived trypomastigotes, and infection percentage. Statistical analyses, including ANOVA tests, identified significant differences. Varying onset times for metacyclogenesis converged on the 7th day. TcI (MG) exhibited the highest metacyclogenesis potential. TcI (DA) stood out, infecting 80% of cells within 24 h. TcI demonstrated the highest potential in both metacyclogenesis and infection among the strains assessed. Intra-DTU diversity was evident among TcI strains, contributing to a comprehensive understanding of Trypanosoma cruzi dynamics and genetic diversity.

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Fifteen Years after the Definition of Trypanosoma cruzi DTUs: What Have We Learned?

Cited by 15 publications

References 185 publications

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes

Comparative analysis of metacyclogenesis and infection curves in different discrete typing units of Trypanosoma cruzi

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