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

BACKGROUND: Chagas 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 inv...

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Autores principales: Mello, Debora B., Ramos, Isalira P., Mesquita, Fernanda C. P., Brasil, Guilherme V., Rocha, Nazareth N., Takiya, Christina M., Lima, Ana Paula C. A., Campos de Carvalho, Antonio C., Goldenberg, Regina S., Carvalho, Adriana B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527728/
https://www.ncbi.nlm.nih.gov/pubmed/26248209
http://dx.doi.org/10.1371/journal.pntd.0003945
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author Mello, Debora B.
Ramos, Isalira P.
Mesquita, Fernanda C. P.
Brasil, Guilherme V.
Rocha, Nazareth N.
Takiya, Christina M.
Lima, Ana Paula C. A.
Campos de Carvalho, Antonio C.
Goldenberg, Regina S.
Carvalho, Adriana B.
author_facet Mello, Debora B.
Ramos, Isalira P.
Mesquita, Fernanda C. P.
Brasil, Guilherme V.
Rocha, Nazareth N.
Takiya, Christina M.
Lima, Ana Paula C. A.
Campos de Carvalho, Antonio C.
Goldenberg, Regina S.
Carvalho, Adriana B.
author_sort Mello, Debora B.
collection PubMed
description BACKGROUND: Chagas 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 FINDINGS: ASC 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/SIGNIFICANCE: In 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.
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spelling pubmed-45277282015-08-12 Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity Mello, Debora B. Ramos, Isalira P. Mesquita, Fernanda C. P. Brasil, Guilherme V. Rocha, Nazareth N. Takiya, Christina M. Lima, Ana Paula C. A. Campos de Carvalho, Antonio C. Goldenberg, Regina S. Carvalho, Adriana B. PLoS Negl Trop Dis Research Article BACKGROUND: Chagas 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 FINDINGS: ASC 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/SIGNIFICANCE: In 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. Public Library of Science 2015-08-06 /pmc/articles/PMC4527728/ /pubmed/26248209 http://dx.doi.org/10.1371/journal.pntd.0003945 Text en © 2015 Mello et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mello, Debora B.
Ramos, Isalira P.
Mesquita, Fernanda C. P.
Brasil, Guilherme V.
Rocha, Nazareth N.
Takiya, Christina M.
Lima, Ana Paula C. A.
Campos de Carvalho, Antonio C.
Goldenberg, Regina S.
Carvalho, Adriana B.
Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity
title Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity
title_full Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity
title_fullStr Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity
title_full_unstemmed Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity
title_short Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity
title_sort adipose tissue-derived mesenchymal stromal cells protect mice infected with trypanosoma cruzi from cardiac damage through modulation of anti-parasite immunity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527728/
https://www.ncbi.nlm.nih.gov/pubmed/26248209
http://dx.doi.org/10.1371/journal.pntd.0003945
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