Related Experiment Video
Updated: May 12, 2026
Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium
Mariela Natacha González1, Nilay Dey, Nisha Jain Garg
1Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben", Ciudad Autónoma de Buenos Aires, Argentina.
Insights
Granulocyte-colony stimulating factor (G-CSF) aids bone marrow stem cell (BMSC) repair in Chagas disease hearts but doesn't clear the parasite. Combined therapy with benznidazole and G-CSF effectively heals heart tissue damage.
Area of Science:
- Cardiovascular Research
- Infectious Diseases
- Regenerative Medicine
Background:
- Chagas disease, caused by Trypanosoma cruzi, commonly leads to cardiomyopathy and heart failure.
- Granulocyte-colony stimulating factor (G-CSF) promotes heart tissue repair via bone marrow stem cell (BMSC) mobilization.
Purpose of the Study:
- To investigate if G-CSF can ameliorate Trypanosoma cruzi-induced myocarditis.
- To evaluate the efficacy of G-CSF in promoting cardiac repair and controlling parasite burden.
Main Methods:
- T. cruzi-infected mice were treated with G-CSF, monitoring parasite load, BMSC mobilization, cytokine profiles, and cardiac remodeling.
- Analysis included assessing stem cell markers (CXCR4, CD34, c-Kit), cardiomyocyte differentiation markers (GATA4, MEF2C, desmin), cytokine levels, extracellular matrix components, and parasite burden.
Main Results:
- G-CSF treatment mobilized BMSCs, with some differentiating into cardiomyocytes, evidenced by increased GATA4(+)/MEF2C(+) and desmin expression.
- G-CSF induced a mixed immune response (IL-10+TGF-β>IFN-γ+TNF-α>IL-4), increasing inflammation without controlling T. cruzi.
- While G-CSF improved extracellular matrix integrity and promoted compensatory remodeling, it did not resolve cardiomyocyte atrophy. Combining benznidazole (BZ) with G-CSF controlled parasitism and inflammation, enabling G-CSF to effectively repair cardiac tissue.
Conclusions:
- G-CSF enhances BMSC migration and differentiation into cardiomyocytes in T. cruzi-infected hearts, but promotes a mixed immune response leading to persistent inflammation.
- G-CSF alone has limited efficacy in controlling T. cruzi infection and restoring cardiac homeostasis.
- Combinatorial therapy using benznidazole followed by G-CSF (BZ → G-CSF) is beneficial for arresting inflammatory processes and mitigating tissue damage in Chagasic hearts.
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, indicating mobilization 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 a mixed 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.
