Immune and Repair Mechanisms Underlying Congenital Chagas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE311812 | GEO | 2026/03/12
REPOSITORIES: GEO
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Project description:Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected parasitic disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and ultimately many of these individuals will progress to advanced heart failure. The mechanism by which this progression occurs is poorly understood, as few studies have focused on early CCC. In this study, we sought to understand the physiologic changes associated with T. cruzi infection and the development of CCC. We analyzed gene expression in the peripheral blood of asymptomatic Chagas patients with early structural heart disease, Chagas patients without any signs or symptoms of disease, and Chagas-negative patients with and without early structural heart disease. Our analysis shows that early CCC was associated with a downregulation of various peripheral immune response genes, with gene expression changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes were distinct from those of early cardiomyopathy in Chagas-negative patients, suggesting that the processes mediating CCC may be unique from those mediating progression to other cardiomyopathies. This work highlights the importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease. The changes we have identified may serve as biomarkers of progression and could inform strategies for the treatment of CCC in its early stages, before significant cardiac damage has occurred.
2024-10-04 | GSE244827 | GEO
Project description:Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease. Background. More than one million women in fertile age are infected with Trypanosoma cruzi worldwide. Anti-T.cruzi seropositivity in mothers has been associated with adverse pregnancy outcome but there is still a knowledge gap regarding this effect. Our aim was to compare the gene expression profile of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers. Methods. A RNA-Seq was performed in 9 pools of 2 different placental RNA samples each: 3 belonging to placentas from SN and 6 from SP. Each pool consisted of a binomial of a female/male newborn and a vaginal/caesarean delivery. None of the newborns resulted infected. Results. Only 42 genes showed a significant fold change between SP and SN groups. Among the down-regulated genes were KISS1 and CGB5. In the up-regulated genes group were: KIF12, HLA-G, PRG2, TAC3, FN1 and ATXN3L. To identify pathways significantly associated with maternal T. cruzi-infection, a gene-set association analysis was implemented. The placental environment transcriptomic profile of SP consisted of an enrichment in immunological genes sets (inflammatory response and lymphocytic activation were over-expressed) whereas numerous biosynthetic processes were down-regulated. Conclusions. It is worth noting that several differentially expressed genes in SP placentas code for proteins associated to preeclampsia and miscarriage. This first transcriptomics study in human term placental environment from non-infected deliveries shows a placental response that may affect the faetus while protecting it from the parasite infection; this host response could be responsible for the low rate of congenital transmission observed in human chronic Chagas disease.
2018-02-20 | GSE107376 | GEO
Project description:Chagas’ disease, one of the major public health concerns in Latin America, is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). In the past few years congenital transmission of T. cruzi has become more important, and partly responsible for the “globalization of Chagas’ disease”. The congenital transmission, although with low rates, represents the main route of transmission in non-endemic countries and endemic countries without vectorial transmission, and represents one third of the new cases each year. Diverse pathogens, including T. cruzi, are able to cross the placental barrier and infect both the placenta and fetus. However, the exact cellular and molecular mechanisms of host-pathogen interaction between T. cruzi and the placenta has been scarcely studied. The use of microarray analysis to determine expression profiles constitutes a powerful tool in order to identify genes and pathways related to the host response to infections. Here, we analyzed the transcriptomic response of human placental chorionic villi explants (HPCVE) challenged with T. cruzi trypomastigotes at low (105) and high (106) concentrations for 2 and 24 hours
2018-04-17 | GSE113155 | GEO
Project description:We used Affymetrix U133A 2.0 chips to better understand transcriptional changes associated with HIV-1 infection and perinatal transmission in human PBMCS obtained from young adult mothers with infants in Botswana in vivo. HIV seropositive and drug naïve samples: GSM94333, GSM94334, GSM94335, GSM94336, GSM94337, GSM94338, GSM94340, GSM94342, GSM94343, GSM94345, GSM94351, GSM94353, GSM94354, GSM94355, GSM94357, GSM94358, GSM94360, GSM94361, GSM94362, GSM94364, GSM94365, GSM94367, GSM94369, GSM94370, GSM94378 HIV seronegative samples: GSM92590, GSM92788, GSM92789, GSM92790, GSM92791, GSM92792, GSM92793, GSM92794, GSM92795, GSM92796, GSM92797, GSM92798, GSM92799, GSM92800, GSM92801, GSM92802, GSM92803, GSM92804, GSM92805, GSM92806 HIV seropositive transmitter mothers: GSM94333, GSM94334, GSM94335, GSM94336, GSM94337, GSM94338, GSM94340, GSM94342, GSM94343, GSM94345, GSM94378 HIV seropositive nontransmitter mothers: GSM94351, GSM94353, GSM94354, GSM94355, GSM94357, GSM94358, GSM94360, GSM94361, GSM94362, GSM94364, GSM94365, GSM94367, GSM94369, GSM94370 Keywords: Cross-sectional, peripheral host response to HIV-1 infection, transmission associated gene expression.
2006-07-01 | GSE4124 | GEO
Project description:Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation. Certain tryptophan (Trp) metabolites have been identified as AhR ligands with regulatory functions. We investigated AhR expression, agonist response, ligand production, and AhR-dependent responses, such as IDO activation and regulatory T (Treg) cells induction, in two T.cruzi-infected mouse strains (B6 and Balb/c) showing different polymorphisms in AhR. Furthermore, we assessed the metabolic profile of Trp catabolites and AhR agonistic activity levels in plasma samples from patients with chronic Chagas disease (CCD) and healthy donors (HD) using a luciferase reporter assay and liquid chromatography-mass spectrophotometry (LC-MS) analysis. T. cruzi-infected B6 mice showed impaired AhR-dependent responses compared to Balb/c mice, including reduced IDO activity, kynurenine levels, Treg cell induction, CYP1A1 up-regulation, and AhR expression following agonist activation. Additionally, B6 mice exhibited no detectable 34 AhR agonist activity in plasma and displayed lower CYP1A1 up-regulation and AhR expression upon agonist activation. Similarly, CCC patients had decreased AhR agonistic activity in plasma compared to HD patients and exhibited dysregulation in Trp metabolic pathways, resulting in altered plasma metabolite profiles. Notably, patients with severe CCC specifically showed increased N-acetylserotonin levels in their plasma. The methods and findings presented here contribute to a better understanding of CCC development mechanisms and may identify potential specific biomarkers for T. cruzi infection and the severity of associated heart disease. These insights could be valuable in designing new therapeutic strategies. Ultimately, this research aims to establish the AhR agonistic activity and Trp metabolic profile in plasma as an innovative, non-invasive predictor of prognosis for chronic Chagas disease.
2023-10-09 | GSE244478 | GEO
Project description:We used Affymetrix U133A 2.0 chips to better understand transcriptional changes associated with HIV-1 infection and perinatal transmission in human PBMCS obtained from young adult mothers with infants in Botswana in vivo. HIV seropositive and drug naïve samples:; GSM94333, GSM94334, GSM94335, GSM94336, GSM94337, GSM94338, GSM94340, GSM94342, GSM94343, GSM94345, GSM94351, GSM94353, GSM94354, GSM94355, GSM94357, GSM94358, GSM94360, GSM94361, GSM94362, GSM94364, GSM94365, GSM94367, GSM94369, GSM94370, GSM94378; HIV seronegative samples:; GSM92590, GSM92788, GSM92789, GSM92790, GSM92791, GSM92792, GSM92793, GSM92794, GSM92795, GSM92796, GSM92797, GSM92798, GSM92799, GSM92800, GSM92801, GSM92802, GSM92803, GSM92804, GSM92805, GSM92806; HIV seropositive transmitter mothers:; GSM94333, GSM94334, GSM94335, GSM94336, GSM94337, GSM94338, GSM94340, GSM94342, GSM94343, GSM94345, GSM94378; HIV seropositive nontransmitter mothers:; GSM94351, GSM94353, GSM94354, GSM94355, GSM94357, GSM94358, GSM94360, GSM94361, GSM94362, GSM94364, GSM94365, GSM94367, GSM94369, GSM94370 Experiment Overall Design: Total RNA was extracted from peripheral blood and processed for microarray hybridizations that were conducted using U133A 2.0 chips (Affymetrix, Santa Clara, CA). The 22,777 gene-probes were filtered based on presence/absence, resulting in data for 11,705 gene-probes. The array data sets were then analyzed for differential expression based on HIV status (seronegative, seropositive) and transmitter status (transmitter: TR, nontransmitter: NTR) using BADGE version 1.0, a computer program implementing a Bayesian approach to identify differentially expressed genes (Sebastiani et al, Nat.Gen, 2005). Once differentially expressed genes were identified by BADGE, the biologically enriched categories were identified, as recently described (Montano et al, Int Immunol, 2006), by implementing a stand-alone version of the EASE statistical software (Hosack et al, Genome Biol., 2003). Selected genes were validated using realtime reverse transcription PCR.
2008-06-12 | E-GEOD-4124 | biostudies-arrayexpress
Project description:Gene expression profiles in T. cruzi strains isolated from individuals presenting the indeterminate and cardiac forms of Chagas disease. Genetic markers differentially expressed may be of potential use in diagnostic/prognostic tests and could assist the understanding of pathogenesis of Chagas disease Keywords: other
2005-10-08 | GSE1828 | GEO
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology.
2015-09-10 | GSE63083 | GEO
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology.
2015-09-10 | GSE63082 | GEO
Project description:Transcriptome analysis of circulating microRNAs associated with Chagas disease susceptibility and chronic Chagas cardiomyopathy severity
| PRJNA1275016 | ENA