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Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
High fat diet modulates inflammatory parameters in the heart and liver during acute Trypanosoma cruzi infection
Vivian Paulino Figueiredo1, Evandro Saraiva Lopes Junior2, Laís Roquete Lopes3
1Department of Biological Sciences, Ouro Preto, Minas Gerais, Brazil; Post graduation program of Biological Sciences/NUPEB, Ouro Preto, Minas Gerais, Brazil.
Insights
A high-fat diet (HFD) exacerbates Trypanosoma cruzi infection, increasing parasite load and inflammation in the heart and liver. This diet worsens Chagas disease progression and associated cardiac and liver immunopathology.
Area of Science:
- Immunology
- Cardiovascular Biology
- Parasitology
Background:
- High-fat diets (HFD) are linked to metabolic and cardiovascular diseases.
- Trypanosoma cruzi infection causes progressive inflammation affecting vital organs like the heart and liver.
Purpose of the Study:
- To investigate the impact of an HFD on immune response and matrix metalloproteinase (MMP) activity during acute T. cruzi infection.
- To analyze the effects of the cardiac-tropic T. cruzi VL-10 strain on mice fed regular or HFD.
Main Methods:
- Mice were fed regular or HFD for 8 weeks before T. cruzi infection.
- Histology and zymography were used to assess liver and heart tissues on day 30 post-infection.
- Plasma levels of inflammatory mediators (IL-10, TNF, CCL2, CCL5) and MMP-2 activity were measured.
Main Results:
- HFD-fed mice exhibited higher parasitemia, LDL, and total cholesterol.
- Infection elevated inflammatory mediators and cardiac MMP-2 activity, irrespective of diet.
- HFD induced hepatic steatosis, while cardiac leukocyte infiltration occurred in infected mice.
Conclusions:
- HFD intensifies circulating T. cruzi load.
- A high-fat diet promotes cardiac and liver immunopathogenesis during T. cruzi VL-10 infection.
- Dietary fat content significantly influences the host's response to parasitic infection.
Abstract:
The high fat diet (HFD) can trigger metabolic and cardiovascular diseases. Trypanosoma cruzi infection induces progressive inflammatory manifestations capable to affect the structure and the function of important organs such as the heart and liver. Here we aimed to investigate the effects of a HFD on the immune response and matrix metalloproteinase (MMP) activities during acute infection with the T. cruzi strain VL-10. The VL-10 strain has cardiac tropism and causes myocarditis in mice. Male C57BL/6 mice were treated with either: (i) regular diet (Reg) or (ii) HFD for 8 weeks, after which mice in each group were infected with T. cruzi. Mice were euthanized on day 30 after infection, and the liver and heart were subjected to histology and zymography to determine MMP-2 activities and plasma levels of IL-10, TNF, CCL2, and CCL5. T. cruzi-infected HFD animals had higher parasitemia, LDL and total cholesterol levels. Regardless of diet, plasma levels of all inflammatory mediators and cardiac MMP-2 activity were elevated in infected mice in contrast with the low plasma levels of leptin. HFD animals presented micro- and macrovesicular hepatic steatosis, while cardiac leukocyte infiltration was mainly detected in T. cruzi-infected mice. Our findings suggested that a HFD promotes higher circulating T. cruzi load and cardiac and liver immunopathogenesis in an experimental model using the VL-10 strain of the T. cruzi.
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