Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Composition of Immunotherapy
2.3. Mice, Challenge Infection, and Treatment with Immunotherapy
2.4. Flow Cytometry
2.5. Real Time RT-qPCR
2.6. Parasite Burden
2.7. Histology
2.8. Serum Markers of Oxidative Stress and Inflammation
2.9. Western Blotting
2.10. Immunohistochemistry
2.11. Statistical Analysis
3. Results
3.1. Effects of Nano-Immunotherapy on Functional Activation and Recall Response of CD4+T Cells in Chagas Mice
3.2. Effects of Nano-Immunotherapy on Functional Activation and Recall Response of CD8+ T Cells in Chagas Mice
3.3. Splenic Expression of Cytokines in Chagas Mice (± Immunotherapy)
3.4. Parasite Persistence and Inflammatory Pathology (± Nano-Immunotherapy)
3.5. Efficacy of Nano2/4 in Arresting Peripheral and Myocardial Oxidative Stress in Chagas Mice
3.6. Tissue Fibrosis and Profibrotic Macrophages in Chagas Disease (± Nano Therapy)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Immunotherapy | Heart Mean ± SD (Score Range) | Skeletal Muscle Mean ± SD (Score Range) |
---|---|---|
A. Inflammation score | ||
No infection | 0 | 0 |
T. cruzi only | 2.17 ± 0.17*** (0–3) | 2.91 ± 0.08*** (1–3) |
Tc.p2/4 | 0.83 ± 0.11^^^ (0–1) | 1 ± 0^^^ (1) |
Tc.nano2/4 | 0.91 ± 0.08^^^ (0–1) | 0.91 ± 0.08^^^ (0–1) |
B. Fibrosis score | ||
No infection | 0 | 0 |
T. cruzi only | 5.1 ± 0.48*** | 6.4 ± 0.8*** |
Tc.p2/4 | 0.73 ± 0.02^^^ | 0.74 ± 0.6^^^ |
Tc.nano2/4 | 0.4 ± 0.04^^^, & | 0.51 ± 0.05^^^, & |
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Lokugamage, N.; Choudhuri, S.; Davies, C.; Chowdhury, I.H.; Garg, N.J. Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection. Vaccines 2020, 8, 96. https://doi.org/10.3390/vaccines8010096
Lokugamage N, Choudhuri S, Davies C, Chowdhury IH, Garg NJ. Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection. Vaccines. 2020; 8(1):96. https://doi.org/10.3390/vaccines8010096
Chicago/Turabian StyleLokugamage, Nandadeva, Subhadip Choudhuri, Carolina Davies, Imran Hussain Chowdhury, and Nisha Jain Garg. 2020. "Antigen-Based Nano-Immunotherapy Controls Parasite Persistence, Inflammatory and Oxidative Stress, and Cardiac Fibrosis, the Hallmarks of Chronic Chagas Cardiomyopathy, in A Mouse Model of Trypanosoma cruzi Infection" Vaccines 8, no. 1: 96. https://doi.org/10.3390/vaccines8010096