A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction
ABSTRACT Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of T. br...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2025-02-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01623-24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540853882585088 |
|---|---|
| author | Nathan P. Crilly Marcelle Dina Zita Alexander K. Beaver Polina Sysa-Shah Aashik Bhalodia Kathy Gabrielson Luigi Adamo Monica R. Mugnier |
| author_facet | Nathan P. Crilly Marcelle Dina Zita Alexander K. Beaver Polina Sysa-Shah Aashik Bhalodia Kathy Gabrielson Luigi Adamo Monica R. Mugnier |
| author_sort | Nathan P. Crilly |
| collection | DOAJ |
| description | ABSTRACT Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of T. brucei infection. Despite the importance of T. brucei as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of T. brucei-associated cardiomyopathy. We present the first clinically relevant, reproducible murine model of cardiac dysfunction in chronic T. brucei infection. Similar to humans, mice showed histological evidence of myocarditis and elevation of serum NT-proBNP with electrocardiographic abnormalities. Serum NT-proBNP levels were elevated prior to the development of severe ventricular dysfunction. On flow cytometry, myocarditis was associated with an increase of most myocardial immune cell populations, including multiple T cell and macrophage subsets, corroborating the notion that T. brucei-associated cardiac damage is an immune-mediated event. This novel mouse model represents a powerful and practical tool to investigate the pathogenesis of T. brucei-mediated heart damage and supports the development of therapeutic options for T. brucei-associated cardiac disease. In characterizing this model, we provide evidence that T. brucei causes cardiac disease, and we suggest that immunopathology is an important contributor to cardiac pathology. Along with other recent studies, our work demonstrates the importance of extravascular spaces, including the heart, for T. brucei pathogenesis.IMPORTANCEAfrican trypanosomiasis is a neglected tropical disease affecting both people and cattle, which represents a major public health problem in sub-Saharan Africa with an enormous socioeconomic impact. Cardiac disease represents an underappreciated clinical manifestation of African trypanosomiasis that may lead to lifelong illness despite successful treatment of infection. However, this aspect of African trypanosomiasis remains poorly understood, partially due to a lack of well-characterized and practical animal models. In this study, we present the development and characterization of a novel, reproducible, and cost-effective mouse model of cardiac dysfunction in African trypanosomiasis. We demonstrate that this model recapitulates major features of cardiac dysfunction in natural infection, including the presence of parasites in the cardiac interstitial spaces, alterations of cardiac biomarkers, and functional changes. This model represents a resource to support the understanding of cardiac complications of trypanosomiasis and the development of new therapies to prevent and treat cardiac involvement in African trypanosomiasis. |
| format | Article |
| id | doaj-art-333b142163ef4903b3c5dee0c0284b6d |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-333b142163ef4903b3c5dee0c0284b6d2025-02-04T14:03:40ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-02-0113210.1128/spectrum.01623-24A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunctionNathan P. Crilly0Marcelle Dina Zita1Alexander K. Beaver2Polina Sysa-Shah3Aashik Bhalodia4Kathy Gabrielson5Luigi Adamo6Monica R. Mugnier7Department of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USADivision of Cardiology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USADepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USADepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USADivision of Cardiology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USADepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USADivision of Cardiology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USADepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USAABSTRACT Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of T. brucei infection. Despite the importance of T. brucei as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of T. brucei-associated cardiomyopathy. We present the first clinically relevant, reproducible murine model of cardiac dysfunction in chronic T. brucei infection. Similar to humans, mice showed histological evidence of myocarditis and elevation of serum NT-proBNP with electrocardiographic abnormalities. Serum NT-proBNP levels were elevated prior to the development of severe ventricular dysfunction. On flow cytometry, myocarditis was associated with an increase of most myocardial immune cell populations, including multiple T cell and macrophage subsets, corroborating the notion that T. brucei-associated cardiac damage is an immune-mediated event. This novel mouse model represents a powerful and practical tool to investigate the pathogenesis of T. brucei-mediated heart damage and supports the development of therapeutic options for T. brucei-associated cardiac disease. In characterizing this model, we provide evidence that T. brucei causes cardiac disease, and we suggest that immunopathology is an important contributor to cardiac pathology. Along with other recent studies, our work demonstrates the importance of extravascular spaces, including the heart, for T. brucei pathogenesis.IMPORTANCEAfrican trypanosomiasis is a neglected tropical disease affecting both people and cattle, which represents a major public health problem in sub-Saharan Africa with an enormous socioeconomic impact. Cardiac disease represents an underappreciated clinical manifestation of African trypanosomiasis that may lead to lifelong illness despite successful treatment of infection. However, this aspect of African trypanosomiasis remains poorly understood, partially due to a lack of well-characterized and practical animal models. In this study, we present the development and characterization of a novel, reproducible, and cost-effective mouse model of cardiac dysfunction in African trypanosomiasis. We demonstrate that this model recapitulates major features of cardiac dysfunction in natural infection, including the presence of parasites in the cardiac interstitial spaces, alterations of cardiac biomarkers, and functional changes. This model represents a resource to support the understanding of cardiac complications of trypanosomiasis and the development of new therapies to prevent and treat cardiac involvement in African trypanosomiasis.https://journals.asm.org/doi/10.1128/spectrum.01623-24cardiologyparasitologyTrypanosoma bruceiimmunology |
| spellingShingle | Nathan P. Crilly Marcelle Dina Zita Alexander K. Beaver Polina Sysa-Shah Aashik Bhalodia Kathy Gabrielson Luigi Adamo Monica R. Mugnier A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction Microbiology Spectrum cardiology parasitology Trypanosoma brucei immunology |
| title | A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction |
| title_full | A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction |
| title_fullStr | A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction |
| title_full_unstemmed | A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction |
| title_short | A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction |
| title_sort | murine model of trypanosoma brucei induced myocarditis and cardiac dysfunction |
| topic | cardiology parasitology Trypanosoma brucei immunology |
| url | https://journals.asm.org/doi/10.1128/spectrum.01623-24 |
| work_keys_str_mv | AT nathanpcrilly amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT marcelledinazita amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT alexanderkbeaver amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT polinasysashah amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT aashikbhalodia amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT kathygabrielson amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT luigiadamo amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT monicarmugnier amurinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT nathanpcrilly murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT marcelledinazita murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT alexanderkbeaver murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT polinasysashah murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT aashikbhalodia murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT kathygabrielson murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT luigiadamo murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction AT monicarmugnier murinemodeloftrypanosomabruceiinducedmyocarditisandcardiacdysfunction |