Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

Debora B Mello,Regina S Goldenberg,Antonio C Campos De Carvalho,Adriana B Carvalho,Ana Paula C A Lima,Fernanda C P Mesquita,Isalira P Ramos,Nazareth N Rocha,Christina M Takiya,Guilherme V Brasil,Eric Dumonteil

doi:10.1371/journal.pntd.0003945

Abstract

BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi (T.cruzi), is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC) can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy.Methodology/Principal FindingsASC were injected intraperitoneally at 3 days post-infection (dpi). Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV) dilation was prevented in ASC-treated mice.Conclusions/SignificanceIn conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

Highlights

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is a complex systemic disease endemic in Central and South America
Chagas disease is caused by the parasite Trypanosoma cruzi, which is transmitted by kissing bugs in endemic areas located in Central and South America
Since Chagas disease is characterized by intense inflammation and one of the key properties of Mesenchymal stromal cells (MSC) is the modulation of the immune system, our work investigated the effect of injecting MSC in a mouse model of Chagas disease

Summary

Introduction

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is a complex systemic disease endemic in Central and South America. Transmitted by hematophagous triatomine insects, the disease has been receiving attention due to other forms of transmission such as blood transfusions, organ transplantation, ingestion of contaminated food or drinks and congenital transmission [1,2]. These vector-independent forms of contracting Chagas disease are the most common in developed countries, especially in North America, due to immigration of infected individuals from endemic areas [1,2]. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC) can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy

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