Pentoxifylline reverses chronic experimental Chagasic cardiomyopathy in association with repositioning of abnormal CD8+ T-cell response

PLoS Neglected Tropical Diseases
Isabela Resende PereiraJoseli Lannes-Vieira

Abstract

Chronic chagasic cardiomyopathy (CCC), the main clinical sign of Chagas disease, is associated with systemic CD8+ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has immunoregulatory and cardioprotective properties. Here, we tested PTX effects on CD8+ T-cell abnormalities and cardiac alterations using a model of experimental Chagas' heart disease. C57BL/6 mice chronically infected by the Colombian Trypanosoma cruzi strain and presenting signs of CCC were treated with PTX. The downmodulation of T-cell receptors on CD8+ cells induced by T. cruzi infection was rescued by PTX therapy. Also, PTX reduced the frequency of CD8+ T-cells expressing activation and migration markers in the spleen and the activation of blood vessel endothelial cells and the intensity of inflammation in the heart tissue. Although preserved interferon-gamma production systemically and in the cardiac tissue, PTX therapy reduced the number of perforin+ cells invading this tissue. PTX did not alter parasite load, but hampered the progression of heart injury, improving connexin 43 expression and decreasing fibronectin overdeposition. Further, PTX reversed electrical abnorm...Continue Reading

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Citations

Oct 28, 2016·PLoS Pathogens·Glaucia Vilar-PereiraClaudia N Paiva
Dec 18, 2015·Memórias do Instituto Oswaldo Cruz·Glaucia Vilar-PereiraJoseli Lannes-Vieira
Aug 1, 2019·PLoS Neglected Tropical Diseases·Roberto Rodrigues FerreiraMariana Caldas Waghabi
Apr 12, 2018·Current Medicinal Chemistry·Elena AguileraMercedes González
Oct 15, 2019·Trends in Parasitology·Eva V Acosta RodríguezAdriana Gruppi
May 8, 2020·Trends in Cardiovascular Medicine·Cynthia YeungAdrian Baranchuk
Aug 13, 2021·Frontiers in Cellular and Infection Microbiology·Priscila Silva Grijó FaraniOtacilio Cruz Moreira
Nov 20, 2021·Frontiers in Cellular and Infection Microbiology·Luiz Ricardo BerbertAna Rosa Pérez

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Methods Mentioned

BETA
flow cytometry
PCR

Software Mentioned

Scope
AnalySIS AUTO
FCAP Array
Summit
Expression Suite

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