Insights into CX3CL1/Fractalkine during experimental Trypanosoma cruzi infection

Menezes, TatianaPrata; Machado, Bianca Alves Almeida; Toledo, Débora Nonato Miranda de; Santos, Priscilla Vilela dos; Ribeiro, Laís Cristina Gonçalves; Talvani, André

doi:10.1016/j.parint.2021.102530

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…Taken together, both protein and transcriptional profiles associated with the newly identified risk haplotype are enriched for cytokine and immune-related biological pathways, an association that is concordant to what is known about Chagas disease and CCC development from human [ 28 – 30 ] and animal [ 31 , 32 ] studies.…”

Section: Discussionsupporting

confidence: 64%

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature

et al. 2022

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Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/Principal findings We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10−9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302–5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. Conclusions/Significance We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.

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Section: Discussionsupporting

confidence: 64%

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature

et al. 2022

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“…This cytokine seems to be involved in tissue damage in patients with chronic Chagas cardiomyopathy due to its role in maintaining CD8+ T cells [ 44 ]. Therefore, IL-15 and CCL2 are induced by tumor necrosis factor, a key cytokine responsible for the magnificence of the acute and chronic immune responses in mice [ 45 ] and human [ 46 ] infections by T. cruzi . This inflammatory mediator network promotes activation and leukocyte chemotaxis from the blood into the infected tissues to eliminate parasites.…”

Section: Discussionmentioning

confidence: 99%

Theracurmin Modulates Cardiac Inflammation in Experimental Model of Trypanosoma cruzi Infection

et al. 2023

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Theracurmin is a nanoparticle formulation derived from curcumin, a bioactive compound known for its antioxidant and anti-inflammatory properties. Trypanosoma cruzi, the etiological agent of Chagas disease, triggers an intense inflammatory response in mammals and also causes severe tissue damage. To evaluate the immunomodulatory and antiparasitic effects of Theracurmin, Swiss mice were experimentally infected with 103 trypomastigote forms of the Colombian strain of T. cruzi and submitted to daily therapy with 30 mg/kg of Theracurmin. In addition, daily benznidazole therapy (100 mg/kg) was performed as a positive control. We evaluated the systemic and tissue parasitism, the survival and the body mass rate, the release of inflammatory mediators (TNF, IL-6, IL-15, CCL2 and creatine kinase) and the tissue inflammation at day 30 post-infection. Theracurmin therapy reduced the parasitemia curve without altering the animals’ survival rate, and it protected mice from losing body mass. Theracurmin also reduced CCL2 in cardiac tissue, IL-15 in cardiac and skeletal tissue, and plasma CK. Even without effects on TNF and IL-6 production and tissue amastigote nests, Theracurmin reduced the leukocyte infiltrate in both evaluated tissues, even in the case of more effective results observed to the benznidazole treatment. Our data suggest Theracurmin has an immunomodulatory (CCL2, IL-15, CK and tissue leukocyte infiltration) and a trypanocidal effect (on circulating parasites) during experimental infection triggered by the Colombian strain of T. cruzi. Further investigations are necessary to comprehend the Theracurmin role performed in combination with benznidazole or other potential anti-T. cruzi chemical compounds.

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Insights into IL-33 on inflammatory response during in vitro infection by Trypanosoma cruzi

et al. 2022

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Insights into CX3CL1/Fractalkine during experimental Trypanosoma cruzi infection

Cited by 3 publications

References 18 publications

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature

Theracurmin Modulates Cardiac Inflammation in Experimental Model of Trypanosoma cruzi Infection

Insights into IL-33 on inflammatory response during in vitro infection by Trypanosoma cruzi

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