scholarly journals Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

2021 ◽  
Vol 11 ◽  
Author(s):  
Emanuelle de Souza Santos ◽  
Dahara Keyse Carvalho Silva ◽  
Bruna Padilha Zurita Claro dos Reis ◽  
Breno Cardim Barreto ◽  
Carine Machado Azevedo Cardoso ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Cardiac Tissue ◽  
Parasitic Infection ◽  
Future Directions ◽  
Immunomodulatory Agents ◽  
Cell Therapies ◽  
Chagas Cardiomyopathy ◽  
Severe Manifestation ◽  
Rational Alternative ◽  
Inflammatory Profile

Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

scholarly journals Glutamine increases body weight and decreases myocardial damage in Trypanosoma cruzi-infected mice treated with nifurtimox.

2021 ◽  
Vol 23 (1) ◽  
pp. 10-16
Author(s):  
Carmen Marín-Tello ◽  
◽  
César Sánchez-Marín ◽  
Luis Arteaga-Temoche ◽  
◽  
...  
Keyword(s):  
Body Weight ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Rural Areas ◽  
Cardiac Tissue ◽  
Parasitic Infection ◽  
Myocardial Damage ◽  
Glutamine Supplementation ◽  
Histopathological Analysis ◽  
Standard Diet

Chagas disease, a parasitic infection caused by the protist Trypanosoma cruzi, affect the poorest populations, living in remote, rural areas and urban slums. Although this drug is effective against Chagas disease present a number of serious side effects. In residents of high Andean areas with megacolon it can lead to cardiomyopathies. The aim of this study was to investigate whether dietary supplementation with L-glutamine may alleviate some of these symptoms because of its previously observed anti-inflammatory properties. We studied two groups of T. cruzi-infected mice receiving treatment with nifurtimox. One group was fed the standard diet, while the other group’s diet was supplemented with Glutamine. We found that Glutamine supplementation increases body weight (p<0.001), decreases heart mass to body mass ratio (p<0.001), and decreases the number of amastigotes present in cardiac tissue. Additionally, histopathological analysis showed less heart tissue damage in the group that received Glutaminne in their diet. Therefore, our findings suggest that Glutamine supplementation improves nifurtimox treatment outcomes of T. cruzi infection.

Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
Author(s):  
Adriana Egui ◽  
Paola Lasso ◽  
Elena Pérez-Antón ◽  
M. Carmen Thomas ◽  
Manuel Carlos López
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Clinical Status ◽  
Chronic Phase ◽  
Parasite Load ◽  
Chronic Patients ◽  
Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

Major Kinds of Drug Targets in Chagas Disease or American Trypanosomiasis

2019 ◽  
Vol 20 (11) ◽  
pp. 1203-1216 ◽  
Author(s):  
Vilma G. Duschak
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Drug Targets ◽  
Defense Mechanisms ◽  
Cysteine Proteinase ◽  
Parasitic Infection ◽  
Etiologic Agent ◽  
World Health ◽  
American Trypanosomiasis ◽  
Group I

American Trypanosomiasis, a parasitic infection commonly named Chagas disease, affects millions of people all over Latin American countries. Presently, the World Health Organization (WHO) predicts that the number of international infected individuals extends to 7 to 8 million, assuming that more than 10,000 deaths occur annually. The transmission of the etiologic agent, Trypanosoma cruzi, through people migrating to non-endemic world nations makes it an emergent disease. The best promising targets for trypanocidal drugs may be classified into three main groups: Group I includes the main molecular targets that are considered among specific enzymes involved in the essential processes for parasite survival, principally Cruzipain, the major antigenic parasite cysteine proteinase. Group II involves biological pathways and their key specific enzymes, such as Sterol biosynthesis pathway, among others, specific antioxidant defense mechanisms, and bioenergetics ones. Group III includes the atypical organelles /structures present in the parasite relevant clinical forms, which are absent or considerably different from those present in mammals and biological processes related to them. These can be considered potential targets to develop drugs with extra effectiveness and fewer secondary effects than the currently used therapeutics. An improved distinction between the host and the parasite targets will help fight against this neglected disease.

scholarly journals Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanchi Malhotra ◽  
Imran Masood ◽  
Noberto Giglio ◽  
Jay D. Pruetz ◽  
Pia S. Pannaraj
Keyword(s):  
United States ◽  
Differential Diagnosis ◽  
Heart Disease ◽  
Chagas Disease ◽  
Latin American ◽  
Current Knowledge ◽  
Parasitic Infection ◽  
The United States ◽  
Cardiac Complications ◽  
The U.S

Abstract Background Chagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S. Methods We prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience. Results Of 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture. Conclusions Pediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

Involvement of monocytes/macrophages as key factors in the development and progression of cardiovascular diseases

2014 ◽  
Vol 458 (2) ◽  
pp. 187-193 ◽  
Author(s):  
María Fernández-Velasco ◽  
Silvia González-Ramos ◽  
Lisardo Boscá
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Initial Period ◽  
Cardiac Injury ◽  
Key Factors ◽  
Cardiac Damage ◽  
Inflammatory Profile

Emerging evidence points to the involvement of specialized cells of the immune system as key drivers in the pathophysiology of cardiovascular diseases. Monocytes are an essential cell component of the innate immune system that rapidly mobilize from the bone marrow to wounded tissues where they differentiate into macrophages or dendritic cells and trigger an immune response. In the healthy heart a limited, but near-constant, number of resident macrophages have been detected; however, this number significantly increases during cardiac damage. Shortly after initial cardiac injury, e.g. myocardial infarction, a large number of macrophages harbouring a pro-inflammatory profile (M1) are rapidly recruited to the cardiac tissue, where they contribute to cardiac remodelling. After this initial period, resolution takes place in the wound, and the infiltrated macrophages display a predominant deactivation/pro-resolution profile (M2), promoting cardiac repair by mediating pro-fibrotic responses. In the present review we focus on the role of the immune cells, particularly in the monocyte/macrophage population, in the progression of the major cardiac pathologies myocardial infarction and atherosclerosis.

Chagas Disease: Chronic Chagas Cardiomyopathy

2019 ◽  
pp. 100507 ◽  
Author(s):  
Natalia Giraldo Echavarría ◽  
Luis E. Echeverría ◽  
Merrill Stewart ◽  
Catalina Gallego ◽  
Clara Saldarriaga
Keyword(s):  
Chagas Disease ◽  
Chagas Cardiomyopathy

Cell therapies for Chagas disease

Cytotherapy ◽  
2017 ◽  
Vol 19 (11) ◽  
pp. 1339-1349 ◽  
Author(s):  
Adriana Bastos Carvalho ◽  
Regina Coeli Dos Santos Goldenberg ◽  
Antonio Carlos Campos de Carvalho
Keyword(s):  
Chagas Disease ◽  
Cell Therapies

scholarly journals Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing

2021 ◽  
Vol 9 ◽  
Author(s):  
Dharshan Sivaraj ◽  
Kellen Chen ◽  
Arhana Chattopadhyay ◽  
Dominic Henn ◽  
Wanling Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Direct Injection ◽  
Future Directions ◽  
Tissue Properties ◽  
Cell Therapies ◽  
Hydrogel Scaffolds ◽  
Cutaneous Wounds ◽  
Bioactive Scaffolds ◽  
Specific Tissue ◽  
Obesity And Cancer

Cutaneous wounds are a growing global health burden as a result of an aging population coupled with increasing incidence of diabetes, obesity, and cancer. Cell-based approaches have been used to treat wounds due to their secretory, immunomodulatory, and regenerative effects, and recent studies have highlighted that delivery of stem cells may provide the most benefits. Delivering these cells to wounds with direct injection has been associated with low viability, transient retention, and overall poor efficacy. The use of bioactive scaffolds provides a promising method to improve cell therapy delivery. Specifically, hydrogels provide a physiologic microenvironment for transplanted cells, including mechanical support and protection from native immune cells, and cell–hydrogel interactions may be tailored based on specific tissue properties. In this review, we describe the current and future directions of various cell therapies and usage of hydrogels to deliver these cells for wound healing applications.

scholarly journals Bioengineering Approaches to Accelerate Clinical Translation of Stem Cell Therapies Treating Osteochondral Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Meng Wang ◽  
Yixuan Luo ◽  
Yin Yu ◽  
Fei Chen
Keyword(s):  
Mechanical Properties ◽  
Stem Cell ◽  
Recent Progress ◽  
Osteochondral Defect ◽  
Cell Phenotype ◽  
Stem Cell Therapies ◽  
Future Directions ◽  
Cell Therapies ◽  
Osteochondral Repair ◽  
Therapeutic Properties

The osteochondral tissue is an interface between articular cartilage and bone. The diverse composition, mechanical properties, and cell phenotype in these two tissues pose a big challenge for the reconstruction of the defected interface. Due to the availability and inherent regenerative therapeutic properties, stem cells provide tremendous promise to repair osteochondral defect. This review is aimed at highlighting recent progress in utilizing bioengineering approaches to improve stem cell therapies for osteochondral diseases, which include microgel encapsulation, adhesive bioinks, and bioprinting to control the administration and distribution. We will also explore utilizing synthetic biology tools to control the differentiation fate and deliver therapeutic biomolecules to modulate the immune response. Finally, future directions and opportunities in the development of more potent and predictable stem cell therapies for osteochondral repair are discussed.

scholarly journals 3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

2019 ◽  
Author(s):  
Ekram Hossain ◽  
Sharmily Khanam ◽  
Chaoyi Wu ◽  
Sharon Lostracco-Johnson ◽  
Diane Thomas ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Large Intestine ◽  
Large Scale ◽  
Scale Effects ◽  
Parasitic Infection ◽  
Parasite Burden ◽  
Acute Stage ◽  
Disease Tolerance ◽  
Chronic Stage ◽  
Spatially Resolved

AbstractChagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi protozoa. Over 8 million people worldwide are T. cruzi-positive, 20-30% of which will develop cardiomyopathy, megaoesophagus and/or megacolon. The mechanisms leading to gastrointestinal (GI) symptom development are however poorly understood. To address this issue, we systematically characterized the spatial impact of experimental T. cruzi infection on the microbiome and metabolome across the GI tract. The largest microbiota perturbations were observed in the proximal large intestine in both acute and chronic disease, with chronic-stage effects also observed in the cecum. Strikingly, metabolomic impact of acute-to-chronic stage transition differed depending on the organ, with persistent large-scale effects of infection primarily in the oesophagus and large intestine, providing a potential mechanism for GI pathology tropism in CD. Infection particularly affected acylcarnitine and lipid metabolism. Building on these observations, treatment of infected mice with carnitine-supplemented drinking water prevented acute-stage mortality with no changes in parasite burden. Overall, these results identified a new mechanism of disease tolerance in CD, with potential for the development of new therapeutic regimens. More broadly, these results highlight the potential of spatially-resolved metabolomic approaches to provide insight into disease pathogenesis, with translational applications for infectious disease drug development.

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