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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

New Biomarker in Chagas Disease: Extracellular Vesicles Isolated from Peripheral Blood in Chronic Chagas Disease Patients Modulate the Human Immune Response

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Author(s):
Madeira, Rafael Pedro [1, 2] ; Dal'Mas Romera, Lavinia Maria [2] ; de Cassia Buck, Paula [3] ; Mady, Charles [3] ; Ianni, Barbara Maria [3] ; Torrecilhas, Ana Claudia [2]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo UNIFESP, Dept Med, Disciplina Infectol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo UNIFESP, Dept Ciencias Farmaceut, Lab Imunol Celular & Bioquim Fungos & Protozoario, Diadema - Brazil
[3] Univ Sao Paulo, Inst Coracao, Unidade Clin Miocardiopatias, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY RESEARCH; v. 2021, JAN 12 2021.
Web of Science Citations: 0
Abstract

Chagas disease, a neglected tropical disease (NTD) caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), is a major public health problem. It was initially restricted to Latin America, but it is now expanding globally. Host and pathogen interactions are crucial in the establishment of disease, and since 1970, it has been known that eukaryotic cells release extracellular vesicles (EVs), which in turn have an important role in intercellular communication in physiological and pathological conditions. Our study proposed to characterize and compare circulating EVs isolated from the plasma of chronic Chagas disease (CCD) patients and controls. For this, peripheral blood was collected from patients and controls, and mononuclear cells (PBMCs) were isolated and stimulated with parasite EVs, showing that patient cells released fewer EVs than control cells. Then, after plasma separation followed by EV total shedding enrichment, the samples were subjected to ultracentrifugation to isolate the circulating EVs, which then had their size and concentration characterized by nanoparticle tracking analysis (NTA). This showed that patients had a lower concentration of circulating EVs while there were no differences in size, corroborating the in vitro data. Additionally, circulating EVs were incubated with THP-1 cells (macrophages) that, after the interaction, had their supernatant analyzed by ELISA for cytokine detection. In relation to their ability to induce cytokine production, the CCD patient EVs were able to induce a differential production of IFN-gamma and IL-17 in relation to controls, with differences being more evident in earlier/less severe stages of the disease. In summary, a decreased concentration of circulating EVs associated with differential activation of the immunological system in patients with CCD is related to parasite persistence and the establishment of chronic disease. It is also a potential biomarker for monitoring disease progression. (AU)

FAPESP's process: 16/01917-3 - The immunomodulatory role of extracellular vesicles shedding from infected macrophages by the Trypanosoma cruzi.
Grantee:Ana Claudia Trocoli Torrecilhas
Support Opportunities: Regular Research Grants