Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium
Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization,ameliorates T. cruzi-induced myocarditis. Methods and results: T. cruzi-infected C...
| Authors: | , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2013 |
| Country: | Argentina |
| Institution: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repository: | CONICET Digital (CONICET) |
| Language: | English |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/24595 |
| Online Access: | http://hdl.handle.net/11336/24595 |
| Access Level: | Open access |
| Keyword: | Trypanosoma cruzi Granulocyte-colony stimulating factor Stem cell Cardiac repair Chagas disease https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| Summary: | Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization,ameliorates T. cruzi-induced myocarditis. Methods and results: T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden,BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicatingmobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4+/MEF2C+ cells and desmin expression in chagasic hearts. G-CSF enhanced amixed cytokine response (IL-10 + TGF-β > IFN-γ + TNF-α > IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. Conclusions: G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg > Th1 > Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts. |
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