Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy.

Emanuelle De Souza Santos,Carine Machado Azevedo Cardoso,Breno Cardim Barreto,Bruna Padilha Zurita Claro Dos Reis,Ricardo Ribeiro Dos Santos,Cássio Santana Meira,Dahara Keyse Carvalho Silva,Milena Botelho Pereira Soares

doi:10.3389/fcimb.2021.765879

Abstract

Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

Highlights

Chagas disease, caused by Trypanosoma cruzi infection, is a neglected disease classically transmitted to animals and people by hematophagous triatomine vectors (Santos et al, 2020; Mansoldo et al, 2020)
The present review provides an overview of current knowledge regarding the use of immunomodulatory agents for treatment of Chronic Chagas cardiomyopathy (CCC), bringing the challenges and future directions in this field
Acetylsalicylic acid, when tested in a BALB/c mouse model of chronic Chagas disease, decreased cardiac inflammatory infiltrate and cardiac fiber disarrangement (González-Herrera et al, 2017). These effects were associated with known actions of aspirin, which as reduction of thromboxane levels and adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, key molecules for the recruitment of monocytes and lymphocytes, which are involved in CCC pathogenesis (Molina-Berrıó s et al, 2013)

Summary

INTRODUCTION

Chagas disease, caused by Trypanosoma cruzi infection, is a neglected disease classically transmitted to animals and people by hematophagous triatomine vectors (Santos et al, 2020; Mansoldo et al, 2020). Acetylsalicylic acid (aspirin), when tested in a BALB/c mouse model of chronic Chagas disease, decreased cardiac inflammatory infiltrate and cardiac fiber disarrangement (González-Herrera et al, 2017) These effects were associated with known actions of aspirin, which as reduction of thromboxane levels and adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, key molecules for the recruitment of monocytes and lymphocytes, which are involved in CCC pathogenesis (Molina-Berrıó s et al, 2013). Treatment of chagasic C57BL/6, which represents a model of mild CCC, with pentoxifylline reversed electrical abnormalities, decreased the number of inflammatory cells and reduced distances of connexin-43+ gap junctions in the heart It promoted the reduction of fibronectin area and CK-MB activity, markers of heart injury in T. cruzi-infected mice (Pereira et al, 2015). Pentoxifylline ameliorated the heart injury and electrical alterations in T. cruzi-infected C3H/He mice, which present a higher inflammation and heart parasitism than infected C57BL/6 mice, being considered a model of severe CCC

Main Results

I.V. Decreased right ventricular internal diameter

Findings

CONCLUDING REMARKS