Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

Gómez-Olarte, Sergio; Bolaños, Natalia I.; Echeverry, Mariana; Rodríguez, Ayda; Cuéllar, Adriana; Puerta, Concepción J.; Mariño, Alejandro; González, John Mario

doi:10.3389/fimmu.2019.01671

Cited by 29 publications

(21 citation statements)

References 71 publications

(76 reference statements)

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“…31 Moreover, they have reduced capability to present antigens to naive T cells in lymph nodes and thus may serve as tolerogenic cells. 65 Consequently, our current findings that the AIT-induced shift toward the increase in intermediate monocytes and decrease in nonclassical monocytes, together with the decrease in HLA-DR 1 clusters, may indicate the systemic response to limit local inflammation and support locally induced tolerance to allergens.…”

Section: Discussionmentioning

confidence: 56%

Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy

Eljaszewicz

Ruchti

Radzikowska

et al. 2021

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 56%

Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy

Eljaszewicz

Ruchti

Radzikowska

et al. 2021

Journal of Allergy and Clinical Immunology

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“…The establishment of a predominantly systemic inflammatory immune response in individuals infected with T. cruzi seems to be crucial for the development of cardiac pathology (22,29,(45)(46)(47)(48)(49). Here, we described elevated plasma levels of IL-6, IL-2, IL-7, IL-15, IL-17A, and IL-10 in the CCC group, as compared to IDC.…”

Section: Discussionmentioning

confidence: 70%

T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

Neves

Koh

Silva

et al. 2022

Front. Cardiovasc. Med.

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Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.

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“…Future studies to identify biomarkers of Chagas disease progression should be longitudinal in nature. The relationship between microbial composition and other variables involved with the microbiome and disease evolution should be investigated, including serum inflammatory mediators (Keating et al, 2015 ; Gomez-Olarte et al, 2019 ; Medeiros et al, 2019 ), diet (Nagajyothi et al, 2014 ), serum vitamin D levels (Oliveira Junior et al, 2019 ), gene polymorphisms (Reis et al, 2017 ; Carvalho et al, 2019 ), and habits such as exercise (Geraix et al, 2007 ; Alves et al, 2019 ). Other studies relating the gut parasite Blastocystis and microbiome also show that the genus Akkermansia plays a role in human gastrointestinal health.…”

Section: Discussionmentioning

confidence: 99%

Gut Dysbiosis in Chagas Disease. A Possible Link to the Pathogenesis

Souza-Basqueira

Ribeiro

Oliveira

et al. 2020

Front. Cell. Infect. Microbiol.

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Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi. Cardiomyopathy and damage to gastrointestinal tissue are the main disease manifestations. There are data suggesting that the immune response to T. cruzi depends on the intestinal microbiota. We hypothesized that Chagas disease is associated with an altered gut microbiome and that these changes are related to the disease phenotype. The stool microbiome from 104 individuals, 73 with Chagas disease (30 with the cardiac, 11 with the digestive, and 32 with the indeterminate form), and 31 healthy controls was characterized using 16S rRNA amplification and sequencing. The QIIME (Quantitative Insights Into Microbial Ecology) platform was used to analyze the data. Alpha and beta diversity indexes did not indicate differences between the groups. However, the relative abundance of Verrucomicrobia, represented primarily by the genus Akkermansia, was significantly lower in the Chagas disease groups, especially the cardiac group, compared to the controls. Furthermore, differences in the relative abundances of Alistipes, Bilophila, and Dialister were observed between the groups. We conclude that T. cruzi infection results in changes in the gut microbiome that may play a role in the myocardial and intestinal inflammation seen in Chagas disease.

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Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

Cited by 29 publications

References 71 publications

Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy

Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy

T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

Gut Dysbiosis in Chagas Disease. A Possible Link to the Pathogenesis

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