Cardiac Manifestations of Trypanosoma cruzi Infection in a Domestic Dog
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ABSTRACT:
SUBMITTER: Stoner C
PROVIDER: S-EPMC7581647 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Project description:Trypanosoma cruzi, the etiological agent of Chagas diseases, invades the cardiac tissue causing acute myocarditis and heart electrical disturbances. In T. cruzi invasion, the parasite induces [Ca2+]i transients in the host cells, an essential phenomenon for invasion. To date, knowledge on the mechanism that elicits transients of [Ca2+]i during the infection of cardiac myocytes has not been fully characterized. Pannexin1 (Panx1) channel are poorly selective channels found in all vertebrates that serve as a pathway for ATP release. In this article, we demonstrate that T. cruzi infection results in the opening of Panx1 channels in cardiac myocytes. We show that pharmacological blockade of Panx1 channels inhibits T. cruzi-induced [Ca2+]i transients and invasion in cardiac myocytes. Our results indicate that opening of Panx1 channels are required for T. cruzi invasion in cardiac myocytes, and we propose that targeting Panx1 channel could provide new potential therapeutic approaches to treat Chagas disease.
| S-EPMC5928702 | biostudies-literature
Project description:CD43 (leukosialin) is a large sialoglycoprotein abundantly expressed on the surface of most cells from the hematopoietic lineage. CD43 is directly involved in the contact between cells participating in a series of events such as signaling, adherence and host parasite interactions. In this study we examined the role of CD43 in the immune response against Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, a potential life-threatening illness endemic in 21 Latin American countries according to the WHO. The acute stage of infection is marked by intense parasitemia and cardiac tissue parasitism, resulting in the recruitment of inflammatory cells and acute damage to the heart tissue. We show here that CD43-/- mice were more resistant to infection due to increased cytotoxicity of antigen specific CD8+ T cells and reduced inflammatory infiltration in the cardiac tissue, both contributing to lower cardiomyocyte damage. In addition, we demonstrate that the induction of acute myocarditis involves the engagement of CD43 cytoplasmic tripeptide sequence KRR to ezrin-radixin-moiesin cytoskeletal proteins. Together, our results show the participation of CD43 in different events involved in the pathogenesis of T. cruzi infection, contributing to a better overall understanding of the mechanisms underlying the pathogenesis of acute chagasic cardiomyopathy.
| S-EPMC6565700 | biostudies-literature
Project description:Understanding the blood meal patterns of insects that are vectors of diseases is fundamental in unveiling transmission dynamics and developing strategies to impede or decrease human-vector contact. Chagas disease has a complex transmission cycle that implies interactions between vectors, parasites and vertebrate hosts. In Ecuador, limited data on human infection are available; however, the presence of active transmission in endemic areas has been demonstrated. The aim of this study was to determine the diversity of hosts that serve as sources of blood for triatomines in domestic, peridomestic and sylvatic transmission cycles, in two endemic areas of Ecuador (central coastal and southern highland regions). Using conserved primers and DNA extracted from 507 intestinal content samples from five species of triatomines (60 Panstrongylus chinai, 17 Panstrongylus howardi, 1 Panstrongylus rufotuberculatus, 427 Rhodnius ecuadoriensis and 2 Triatoma carrioni) collected from 2006 to 2013, we amplified fragments of the cytb mitochondrial gene. After sequencing, blood meal sources were identified in 416 individuals (146 from central coastal and 270 from southern highland regions), achieving ≥ 95% identity with GenBank sequences (NCBI-BLAST tool). The results showed that humans are the main source of food for triatomines, indicating that human-vector contact is more frequent than previously thought. Although other groups of mammals, such as rodents, are also an available source of blood, birds (particularly chickens) might have a predominant role in the maintenance of triatomines in these areas. However, the diversity of sources of blood found might indicate a preference driven by triatomine species. Moreover, the presence of more than one source of blood in triatomines collected in the same place indicated that dispersal of vectors occurs regardless the availability of food. Dispersal capacity of triatomines needs to be evaluated to propose an effective strategy that limits human-vector contact and, in consequence, to decrease the risk of T. cruzi transmission.
| S-EPMC7825724 | biostudies-literature
Project description:BackgroundChronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection.Methodology and principal findingsHere we investigated the contribution of galectin-1 (Gal-1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T. cruzi infection, particularly in the context of cardiac pathology. We found that exposure of HL-1 cardiac cells to Gal-1 reduced the percentage of infection by two different T. cruzi strains, Tulahuén (TcVI) and Brazil (TcI). In addition, Gal-1 prevented exposure of phosphatidylserine and early events in the apoptotic program by parasite infection on HL-1 cells. These effects were not mediated by direct interaction with the parasite surface, suggesting that Gal-1 may act through binding to host cells. Moreover, we also observed that T. cruzi infection altered the glycophenotype of cardiac cells, reducing binding of exogenous Gal-1 to the cell surface. Consistent with these data, Gal-1 deficient (Lgals1-/-) mice showed increased parasitemia, reduced signs of inflammation in heart and skeletal muscle tissues, and lower survival rates as compared to wild-type (WT) mice in response to intraperitoneal infection with T. cruzi Tulahuén strain.Conclusion/significanceOur results indicate that Gal-1 modulates T. cruzi infection of cardiac cells, highlighting the relevance of galectins and their ligands as regulators of host-parasite interactions.
| S-EPMC4599936 | biostudies-literature
Project description:Trypanosoma cruzi infection is a major cause of cardiomyopathy. Gene profiling studies of hearts from infected mice have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 hr post-infection. Statistical comparison of gene expression levels of 2,258 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected (p < 0.05) significant > 1.5 absolute fold changes in 221 (8.8%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. While changes in extracellular matrix and cell adhesion genes were anticipated, modulation of immune response genes in the infected myocytes was surprising. These findings on infected cardiac myocytes in culture reveal that altered gene expression described in the heart in Chagas disease are the consequence of both direct infection of the myocytes and resulting from presence of other cell types in the myocardium and systemic effects of infection.
2009-08-04 | GSE17330 | GEO
Project description:Single-probe single cell mass spectrometry (SCMS) analysis contains 3 sets of experiments:
1. SCMS analysis of 4 groups of cells: infected, bystanders, stained and control cells
2. SCMS analysis of 3 groups of cells (2 replicates): infected, correctly classified bystander, misclassified bystander cells.
3. SCMS-MS of 5 glycerophosphocholines at m/z 768.583, 780.5460, 782.5630, 808.5770 and 810.5940 that were acquired from individual HeLa cells.
2022-05-20 | MSV000089503 | MassIVE
Project description:Trypanosoma cruzi infection is a major cause of cardiomyopathy. Previous gene profiling studies of infected mouse hearts have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 h post-infection. Statistical comparison of gene expression levels of 7624 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected substantial (>or=1.5 absolute fold changes) in 420 (5.5%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. These findings on infected cardiac myocytes in culture reveal that alterations in cardiac gene expression described in Chagas disease are the consequence of both direct infection of the myocytes themselves as well as resulting from the presence of other cell types in the myocardium and systemic effects of infection.
| S-EPMC2825022 | biostudies-literature
Project description:Trypanosoma cruzi infection is a major cause of cardiomyopathy. Gene profiling studies of hearts from infected mice have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 hr post-infection. Statistical comparison of gene expression levels of 2,258 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected (p < 0.05) significant > 1.5 absolute fold changes in 221 (8.8%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. While changes in extracellular matrix and cell adhesion genes were anticipated, modulation of immune response genes in the infected myocytes was surprising. These findings on infected cardiac myocytes in culture reveal that altered gene expression described in the heart in Chagas disease are the consequence of both direct infection of the myocytes and resulting from presence of other cell types in the myocardium and systemic effects of infection. Transcriptomic alteration in neonatal mouse cultured cardiomyocytes induced by the parasite T.cruzi were detected by profiling and compared using AECOM mouse 32k oligonucleotide arrays hybridized in the "multiple yellow" strategy described in Iacobas et al, Biochem Biophys Res Commun. 2006 349(1):329-38.
2010-05-15 | E-GEOD-17330 | biostudies-arrayexpress
Project description:Infection with the zoonotic vector-borne protozoal parasite Trypanosoma cruzi causes Chagas disease in humans and dogs throughout the Americas. Despite the recognized importance of various wildlife species for perpetuating Trypanosoma cruzi in nature, relatively little is known about the development of cardiac disease in infected wildlife. Using a cross-sectional study design, we collected cardiac tissue and blood from hunter-donated wildlife carcasses- including raccoon (Procyon lotor), coyote (Canis latrans), gray fox (Urocyon cinereoargenteus), and bobcat (Lynx rufus) - from central Texas, a region with established populations of infected triatomine vectors and increasing diagnoses of Chagas disease in domestic dogs. Based on PCR analysis, we found that 2 bobcats (14.3%), 12 coyotes (14.3%), 8 foxes (13.8%), and 49 raccoons (70.0%) were positive for T. cruzi in at least one sample (right ventricle, apex, and/or blood clot). Although a histologic survey of right ventricles showed that 21.1% of 19 PCR-positive hearts were characterized by mild lymphoplasmocytic infiltration, no other lesions and no amastigotes were observed in any histologic section. DNA sequencing of the TcSC5D gene revealed that raccoons were infected with T. cruzi strain TcIV, and a single racoon harbored a TcI/TcIV mixed infection. Relative to other wildlife species tested here, our data suggest that raccoons may be important reservoirs of TcIV in Texas and a source of infection for indigenous triatomine bugs. The overall high level of infection in this wildlife community likely reflects high levels of vector contact, including ingestion of bugs. Although the relationship between the sylvatic cycle of T. cruzi transmission and human disease risk in the United States has yet to be defined, our data suggest that hunters and wildlife professionals should take precautions to avoid direct contact with potentially infected wildlife tissues.
| S-EPMC4900435 | biostudies-literature
Project description:Chagas disease resulting from Trypanosoma cruzi infection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. Antiparasitic treatment with benznidazole does not prevent disease progression or death in patients with established cardiac disease. Our consortium is developing a therapeutic vaccine based on the T. cruzi flagellar-derived antigen Tc24-C4 formulated with a Toll-like receptor 4 agonist adjuvant, to complement existing chemotherapy and improve treatment efficacy. Here we demonstrate that therapeutic treatment of acutely infected mice with a reduced dose of benznidazole concurrently with vaccine treatment - also known as "vaccine-linked chemotherapy"-induced a TH17 like immune response, with significantly increased production of antigen specific IL-17A, IL-23 and IL-22, and CD8 + T lymphocytes, as well as significantly increased T. cruzi specific IFNγ-producing CD4 + T lymphocytes. Significantly reduced cardiac inflammation, fibrosis, and parasite burdens and improved survival were achieved by vaccine-linked chemotherapy and individual treatments. Importantly, low dose treatments were comparably efficacious to high dose treatments, demonstrating potential dose sparing effects. We conclude that through induction of TH17 immune responses vaccine-linked chemotherapeutic strategies could bridge the tolerability and efficacy gaps of current drug treatment in Chagasic patients.
| S-EPMC7865072 | biostudies-literature