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Trypanosoma cruzi infection in Cyclophilin D deficient mice
Natalia Milduberger1, Patricia L Bustos1, Carolina González2
1Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben" - ANLIS C. G. Malbrán, Paseo Colón 568, PC 1063, Buenos Aires, Argentina.
Insights
Mice lacking Cyclophilin D (CyPD) showed reduced Trypanosoma cruzi infection. This suggests targeting CyPD could mitigate Chagas disease severity by inhibiting parasite spread.
Area of Science:
- Mitochondrial biology
- Parasitology
- Immunology
Background:
- Chagas disease, caused by Trypanosoma cruzi, frequently impacts the heart.
- Mitochondria are vital for cardiac energy and Cyclophilin D (CyPD) regulates mitochondrial permeability.
- CyPD's role in T. cruzi infection is not fully understood.
Purpose of the Study:
- To investigate the role of Cyclophilin D (CyPD) in Trypanosoma cruzi infection.
- To determine if CyPD deficiency impacts parasite load and cellular infection in mice.
Main Methods:
- Infection of CyPD-deficient (Ppif-/-) and wild-type mice with T. cruzi.
- Quantification of parasite load using PCR in cardiac and skeletal tissues.
- In vitro assessment of cardiomyocyte and macrophage infection.
Main Results:
- Significantly lower T. cruzi parasite loads were observed in cardiac and skeletal tissues of Ppif-/- mice.
- Reduced percentage of infected cells and intracellular parasites in CyPD-deficient cardiomyocytes and macrophages.
- No significant differences in cardiac histopathology or cytokine mRNA between infected groups due to Ppif gene ablation.
Conclusions:
- Mitochondrial CyPD deficiency reduces Trypanosoma cruzi parasite load and cellular infection.
- Inhibiting mitochondrial membrane potential collapse via CyPD ablation may decrease Chagas disease severity.
- CyPD is a potential target for managing T. cruzi infections.
Abstract:
Trypanosoma cruzi is the causative agent of Chagas disease, which is endemic in Latin America and around the world through mother to child transmission. The heart is the organ most frequently affected in the chronic stage of the human infection and depends on mitochondria for the required energy for its activity. Cyclophilins are involved in protein folding and the mitochondrial isoform, Cyclophilin D (CyPD), has a crucial role in the opening of the mitochondrial permeability transition pore. In the present study, we infected CyPD deficient mice, with ablation of the Ppif gene, with T. cruzi parasites and the course of the infection was analyzed. Parasite load, quantified by PCR, was significantly lower in skeletal and cardiac tissues of Ppif-/- mice compared to wild type mice. In vitro cultured cardiomyocytes and macrophages from mice lacking CyPD exhibited lower percentage of infected cells and number of intracellular parasites than those observed for wild type mice. Although histopathological analysis of heart and mRNA of heart cytokines showed differences between T. cruzi-infected mice compared to the uninfected animals, no significant differences were found mice due to the ablation of the Ppif gene. Our results suggest that cells deficient for mitochondrial CyPD, inhibited for the mitochondrial membrane potential collapse, reduces the severity of parasite aggression and spread of cellular infection.
