scholarly journals Differential modulation of mouse heart gene expression by infection with twoTrypanosoma cruzistrains: a transcriptome analysis

2019 ◽  
Author(s):  
TBR Castro ◽  
MCC Canesso ◽  
M Boroni ◽  
DF Chame ◽  
D de Laet Souza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Protein Synthesis ◽  
Immune System ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Host Gene Expression ◽  
Chronic Stage ◽  
Expression Of Genes ◽  
Expression Modulation

The protozoanTrypanosoma cruzi(T. cruzi) is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host andT. cruziare highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important challenge in the field of Chagas disease research is determining the main factors leading to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive system. Our group previously showed that distinct strains ofT. cruzi(JG and Col1.7G2) acquired differential tissue distribution in the chronic stage in dually-infected BALB/c mice. To investigate changes in the host triggered by the two distinctT. cruzistrains, we assessed the gene expression profile of BALB/c mouse hearts infected with either JG, Col1.7G2 or an equivalent mixture of both parasites during the initial phase of infection. This study demonstrates a clear distinction in host gene expression modulation by both parasites. Col1.7G2 strongly activated Th1-polarized immune signature genes, whereas JG showed only minor activation of the host immune response. Moreover, JG strongly reduced the expression of genes for ribosomal proteins and mitochondrial proteins related to the electron transport chain. Interestingly, evaluation of gene expression in mice inoculated with the mixture of parasites showed expression profiles for both up- and down-regulated genes, indicating the coexistence of both parasite strains in the heart during the acute phase. This study suggests that different strains ofT. cruzimay be distinguished by their efficiency in activating the immune system, modulating host energy and reactive oxygen species production and decreasing protein synthesis during early infection, which may be crucial in defining parasite persistence in specific organs.Author SummaryThe causative agent of Chagas disease,Trypanosoma cruzi, retains high genetic diversity, and its populations vary greatly across geographic locations. TheT. cruzimammalian hosts, including humans, also have high genetic variation, making it difficult to predict the disease outcome. Accordingly, this variability must be taken into account in several studies aiming to interrogate the effect of polyparasitism in drug trials, vaccines, diagnosis or basic research. Therefore, there is a growing need to consider the interaction between the pathogen and the host immune system in mixed infections. In the present work, we present an in-depth analysis of the gene expression of hearts from BALB/c mice infected with Col1.7G2 and JG alone or a mixture of both strains. Col1.7G2 induced a higher Th1 inflammatory response, while JG exhibited a weaker activation of immune response genes. Furthermore, JG-infected mice showed a notable reduction in the expression of genes responsible for mitochondrial oxidative phosphorylation and protein synthesis. Interestingly, the mixture-infected group displayed changes in gene expression as caused by both strains. Overall, we provided new insights into the host-pathogen interaction in the context of single and dual infection, showing remarkable differences in host gene expression modulation by twoT. cruzistrains.

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.

scholarly journals Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Criado-Mesas ◽  
N. Abdelli ◽  
A. Noce ◽  
M. Farré ◽  
J. F. Pérez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Barrier Function ◽  
Nutrient Transport ◽  
Gene Expression Pattern ◽  
Vaccine Dose ◽  
Special Focus ◽  
Intestinal Health ◽  
Barrier Failure ◽  
Expression Of Genes

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.

scholarly journals The Liver and the Hepatic Immune Response in Trypanosoma cruzi Infection, a Historical and Updated View

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1074
Author(s):  
Natalia Vacani-Martins ◽  
Marcelo Meuser-Batista ◽  
Carina de Lima Pereira dos Santos ◽  
Alejandro Marcel Hasslocher-Moreno ◽  
Andrea Henriques-Pons
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Clinical Signs ◽  
Cell Types ◽  
Experimental Models ◽  
Chronic Patients ◽  
The Usa ◽  
Multiple Cell ◽  
Underlying Mechanisms

Chagas disease was described more than a century ago and, despite great efforts to understand the underlying mechanisms that lead to cardiac and digestive manifestations in chronic patients, much remains to be clarified. The disease is found beyond Latin America, including Japan, the USA, France, Spain, and Australia, and is caused by the protozoan Trypanosoma cruzi. Dr. Carlos Chagas described Chagas disease in 1909 in Brazil, and hepatomegaly was among the clinical signs observed. Currently, hepatomegaly is cited in most papers published which either study acutely infected patients or experimental models, and we know that the parasite can infect multiple cell types in the liver, especially Kupffer cells and dendritic cells. Moreover, liver damage is more pronounced in cases of oral infection, which is mainly found in the Amazon region. However, the importance of liver involvement, including the hepatic immune response, in disease progression does not receive much attention. In this review, we present the very first paper published approaching the liver’s participation in the infection, as well as subsequent papers published in the last century, up to and including our recently published results. We propose that, after infection, activated peripheral T lymphocytes reach the liver and induce a shift to a pro-inflammatory ambient environment. Thus, there is an immunological integration and cooperation between peripheral and hepatic immunity, contributing to disease control.

scholarly journals In Vivo Analysis of Trypanosoma cruzi Persistence Foci at Single-Cell Resolution

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Alexander I. Ward ◽  
Michael D. Lewis ◽  
Archie A. Khan ◽  
Conor J. McCann ◽  
Amanda F. Francisco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Immune Response ◽  
Smooth Muscle ◽  
Trypanosoma Cruzi ◽  
Parasite Burden ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Chronic Infections ◽  
Content Type ◽  
Chronic Stage

ABSTRACT Infections with Trypanosoma cruzi are usually lifelong despite generating a strong adaptive immune response. Identifying the sites of parasite persistence is therefore crucial to understanding how T. cruzi avoids immune-mediated destruction. However, this is a major technical challenge, because the parasite burden during chronic infections is extremely low. Here, we describe an integrated approach involving comprehensive tissue processing, ex vivo imaging, and confocal microscopy, which allowed us to visualize infected host cells in murine tissue with exquisite sensitivity. Using bioluminescence-guided tissue sampling, with a detection level of <20 parasites, we showed that in the colon, smooth muscle myocytes in the circular muscle layer are the most common infected host cell type. Typically, during chronic infections, the entire colon of a mouse contains only a few hundred parasites, often concentrated in a small number of cells each containing >200 parasites, which we term mega-nests. In contrast, during the acute stage, when the total parasite burden is considerably higher and many cells are infected, nests containing >50 parasites are rarely found. In C3H/HeN mice, but not BALB/c mice, we identified skeletal muscle as a major site of persistence during the chronic stage, with most parasites being found in large mega-nests within the muscle fibers. Finally, we report that parasites are also frequently found in the skin during chronic murine infections, often in multiple infection foci. In addition to being a site of parasite persistence, this anatomical reservoir could play an important role in insect-mediated transmission and have implications for drug development. IMPORTANCE Trypanosoma cruzi causes Chagas disease, the most important parasitic infection in Latin America. Major pathologies include severe damage to the heart and digestive tract, although symptoms do not usually appear until decades after infection. Research has been hampered by the complex nature of the disease and technical difficulties in locating the extremely low number of parasites. Here, using highly sensitive imaging technology, we reveal the sites of parasite persistence during chronic-stage infections of experimental mice at single-cell resolution. We show that parasites are frequently located in smooth muscle cells in the circular muscle layer of the colon and that skeletal muscle cells and the skin can also be important reservoirs. This information provides a framework for investigating how the parasite is able to survive as a lifelong infection, despite a vigorous immune response. It also informs drug development strategies by identifying tissue sites that must be accessed to achieve a curative outcome.

scholarly journals Targeting the Gut Microbiota in Chagas Disease: What Do We Know so Far?

2020 ◽  
Vol 11 ◽  
Author(s):  
Eduardo Duarte-Silva ◽  
Livia H. Morais ◽  
Gerard Clarke ◽  
Wilson Savino ◽  
Christina Peixoto
Keyword(s):  
Immune Response ◽  
Gut Microbiota ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Current Data ◽  
Review Article ◽  
Microbiota Composition ◽  
Comorbid Conditions ◽  
Therapeutic Approaches ◽  
Gut Microbiota Composition

Chagas disease (CD) is a tropical and still neglected disease caused by Trypanosoma cruzi that affects &gt;8 million of people worldwide. Although limited, emerging data suggest that gut microbiota dysfunction may be a new mechanism underlying CD pathogenesis. T. cruzi infection leads to changes in the gut microbiota composition of vector insects, mice, and humans. Alterations in insect and mice microbiota due to T. cruzi have been associated with a decreased immune response against the parasite, influencing the establishment and progression of infection. Further, changes in the gut microbiota are linked with inflammatory and neuropsychiatric disorders, comorbid conditions in CD. Therefore, this review article critically analyses the current data on CD and the gut microbiota of insects, mice, and humans and discusses its importance for CD pathogenesis. An enhanced understanding of host microbiota will be critical for the development of alternative therapeutic approaches to target CD, such as gut microbiota-directed interventions.

scholarly journals Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly SensitiveIn VivoImaging

2015 ◽  
Vol 59 (8) ◽  
pp. 4653-4661 ◽  
Author(s):  
Amanda Fortes Francisco ◽  
Michael D. Lewis ◽  
Shiromani Jayawardhana ◽  
Martin C. Taylor ◽  
Eric Chatelain ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Imaging System ◽  
Ex Vivo ◽  
Parasite Burden ◽  
Significant Activity ◽  
Content Type ◽  
Chronic Stage

ABSTRACTThe antifungal drug posaconazole has shown significant activity againstTrypanosoma cruziin vitroand in experimental murine models. Despite this, in a recent clinical trial it displayed limited curative potential. Drug testing is problematic in experimental Chagas disease because of difficulties in demonstrating sterile cure, particularly during the chronic stage of infection when parasite burden is extremely low and tissue distribution is ill defined. To better assess posaconazole efficacy against acute and chronic Chagas disease, we have exploited a highly sensitive bioluminescence imaging system which generates data with greater accuracy than other methods, including PCR-based approaches. Mice inoculated with bioluminescentT. cruziwere assessed byin vivoandex vivoimaging, with cyclophosphamide-induced immunosuppression used to enhance the detection of relapse. Posaconazole was found to be significantly inferior to benznidazole as a treatment for both acute and chronicT. cruziinfections. Whereas 20 days treatment with benznidazole was 100% successful in achieving sterile cure, posaconazole failed in almost all cases. Treatment of chronic infections with posaconazole did however significantly reduce infection-induced splenomegaly, even in the absence of parasitological cure. The imaging-based screening system also revealed that adipose tissue is a major site of recrudescence in mice treated with posaconazole in the acute, but not the chronic stage of infection. Thisin vivoscreening model for Chagas disease is predictive, reproducible and adaptable to diverse treatment schedules. It should provide greater assurance that drugs are not advanced prematurely into clinical trial.

scholarly journals Insulin resistance in obese adolescents affects the expression of genes associated with immune response

2019 ◽  
Vol 53 (2) ◽  
pp. 71-82 ◽  
Author(s):  
Dmytro O. Minchenko
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Immune Response ◽  
Expression Level ◽  
Control Group ◽  
Gene Expressions ◽  
Down Regulation ◽  
Metabolic Complications ◽  
Obese Adolescents ◽  
Expression Of Genes

AbstractObjective. The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes through changes in the expression of numerous regulatory genes.Methods. The expression level of HLA-DRA, HLA-DRB1, HLA-G, HLA-F, and NFX1 genes as well as miR-190b was measured in the blood of obese adolescents without signs of resistance to insulin and with insulin resistance in comparison with the group of relative healthy control individuals without signs of obesity.Results. It was shown that obesity without signs of insulin resistance is associated with upregulation of the expression level of HLA-DRA and HLA-DRB1 genes, but with down-regulation of HLA-G gene expression in the blood as compared to control group of relative healthy adolescents. At the same time, no significant changes were observed in the expression level of HLA-F and NFX1 genes in the blood of this group of obese adolescents. Development of insulin resistance in obese individuals leads to significant down-regulation of HLA-DRA, HLA-DRB1, HLA-G, and HLA-F gene expressions as well as to up-regulation of NFX1 gene as well as microRNA miR-190b in the blood as compared to obese patients without signs of insulin resistance.Conclusions. Results of this study provide evidence that obesity affects the expression of the subset of genes related to immune response in the blood and that development of insulin resistance in obese adolescents is associated with strong down-regulation of the expressions of HLA-DRA, HLA-DRB1, HLA-F, and HLA-G genes, which may be contribute to the development of obesity complications. It is possible that transcription factor NFX1 and miR-190b participate in downregulation of HLA-DRA gene expression in the blood of obese adolescents with insulin resistance.

Characterization of human infection by Leishmania spp. in the Northwest of Argentina: immune response, double infection with Trypanosoma cruzi and species of Leishmania involved

Parasitology ◽  
2003 ◽  
Vol 126 (1) ◽  
pp. 31-39 ◽  
Author(s):  
F. M. FRANK ◽  
M. M. FERNÁNDEZ ◽  
N. J. TARANTO ◽  
S. P. CAJAL ◽  
R. A. MARGNI ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Human Infection ◽  
Double Infection ◽  
Strong Immune Response ◽  
American Tegumentary Leishmaniasis ◽  
Leishmania Spp ◽  
Very High

The aims of this study were to characterize human American tegumentary leishmaniasis, which includes cutaneous, mucocutaneous and mucosal leishmaniasis, in Northwest Argentina, to determine the prevalence of double infection with Trypanosoma cruzi and to identify the species of Leishmania in this area. Most of the 330 leishmaniasis patients presented cutaneous ulcers (96·1%), 2·4% mucocutaneous and 1·5% the mucosal form (‘espundia’). The aetiological agents, determined by isoenzyme electrophoresis, were identified as Leishmania (Viannia) braziliensis in 16 out of 20 isolates and in the remaining 4 as Leishmania (Leishmania) amazonensis, the first ever-documented in Argentina. Sera analysed by ELISA and IFA using complex antigen from both T. cruzi and L. braziliensis showed a very high percentage of positives (66·3–78·2%). When antigens for specific diagnosis of Chagas' disease were used, 40·9% of the leishmaniasis patients were also found to be infected by T. cruzi. These results indicate that the strong immune response against T. cruzi gave no protection to Leishmania, in spite of the serological cross-reaction between these parasites. In addition, we showed that more than 40% of the patients would be misdiagnosed as chagasic if complex antigens, as epimastigotes or soluble fraction from epimastigotes, were used in IFA or ELISA. This is of paramount importance not only because patients' treatment would be associated to misdiagnosis but the fact that in many countries in Central and South America, a positive test for Chagas' disease means a rejection for those seeking employment.

Changes of RAPD profile of Trypanosoma cruzi II with Canova and Benznidazole

Homeopathy ◽  
2008 ◽  
Vol 97 (02) ◽  
pp. 59-64 ◽  
Author(s):  
Denise Lessa Aleixo ◽  
Fabiana Nabarro Ferraz ◽  
Carolina Sundin de Melo ◽  
Mônica Lúcia Gomes ◽  
Max Jean Toledo ◽  
...  
Keyword(s):  
Immune System ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Saline Solution ◽  
Polyacrylamide Gel ◽  
Control Group ◽  
Genetic Lineage ◽  
Rapd Profile ◽  
Random Amplification ◽  
Liver Infusion Tryptose

Chagas disease, caused by the protozoan Trypanosoma cruzi, involves immunomediated processes. Canova (CA) is a homeopathic treatment indicated in the diseases in which the immune system is depressed. This study evaluated the Random Amplification of Polymorphic DNA (RAPD) profile of T. cruzi under the influence of CA and Benznidazole (BZ). Mice infected with the genetic lineage of T. cruzi II (Y strain) were divided into 4 groups:Infected animals treated with saline solution (control group); treated with CA; treated with BZ; treated with CA and BZ combined.Treatment was given at the 5th–25th days of infection (D5–25). The parasites were isolated by haemoculture in Liver Infusion Tryptose (LIT) medium: at D5 (before treatment), D13, 15 and 25 (during treatment) and D55 and 295 (after treatment). DNA was extracted from the mass of parasites. RAPD was done with the primers λgt11-F, M13F-40 and L15996, the amplified products were eletrophoresed through a 4% polyacrylamide gel. Data were analyzed by the coefficient of similarity using the DNA-POP program.163 markers were identified, 5 of them monomorphic. CA did not act against the parasites when used alone. The RAPD profiles of parasites treated with BZ and CA + BZ were different from those in the control group and in the group treated with CA. The actions of the CA and BZ were different and the action of BZ was different from the action of CA + BZ. These data suggest that CA may interact with BZ. The differences in the RAPD profile of the Y strain of T. cruzi produced by BZ, CA + BZ and the natural course of the infection suggest selection/suppression of populations.

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