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Cytokine profiles during experimental Chagas' disease
M J Morato1, D G Colley, M R Powell
1Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Brasil.
Insights
DBA/2 mice infected with Trypanosoma cruzi show enhanced immune responses, including higher cytokine production, correlating with severe cardiomyopathy. B10.D2 mice exhibit a different immune profile, suggesting distinct immunological parameters influence Chagas disease severity.
Area of Science:
- Immunology
- Parasitology
- Cardiovascular Research
Background:
- Trypanosoma cruzi infection leads to Chagas disease, with variable cardiomyopathy development.
- Murine models (DBA/2 vs. B10.D2) display differential susceptibility to T. cruzi-induced cardiac damage.
Purpose of the Study:
- To investigate immunological differences, specifically cytokine production, between susceptible (DBA/2) and resistant (B10.D2) mice during T. cruzi infection.
- To correlate these immune changes with the severity of cardiac pathology.
Main Methods:
- Comparison of spleen cell cytokine production (IFN-gamma, IL-10, IL-4) after Concanavalin A stimulation in acute and chronic T. cruzi infection phases.
- Assessment of spleen cell proliferative responses to Con A stimulation.
- Correlation of immunological data with observed cardiomyopathy.
Main Results:
- DBA/2 mice maintained high IFN-gamma production in chronic infection, unlike B10.D2 mice.
- DBA/2 mice showed significantly higher IL-10 and IL-4 production, especially in the acute phase.
- Elevated IL-4 levels persisted and increased in chronic DBA/2 infection.
- DBA/2 mice exhibited significantly higher spleen cell proliferation in both infection phases.
Conclusions:
- Enhanced immune responses, including elevated cytokines and proliferation, in DBA/2 mice correlate with severe cardiomyopathy.
- These immune differences may be linked to parasite burden, impaired down-regulation, or autoimmune processes.
- The study highlights key immunological parameters influencing Chagas disease pathogenesis.
Abstract:
People infected with Trypanosoma cruzi remain so for life, yet only 30-40% of these individuals develop characteristic chagasic cardiomyopathies. Similarly, when infected with the Brazilian strain of T. cruzi, DBA/2 mice develop severe cardiac damage while B10.D2 mice do not. To better understand the immunological parameters that may be involved in the disease process, we have used this murine model (DBA/2 vs B10.D2) and compared the changes in cytokine production during the course of infection with T cruzi. Concanavalin A (Con A) stimulation of spleen cells harvested during the acute phase (day 30) resulted in similarly high levels of IFN-gamma in both mouse strains. However, the amount of IFN-gamma in supernatants from cultures of B10.D2 spleen cells initiated during the chronic phase (day 72) was at subacute levels, whereas secretion by chronic DBA/2 spleen cells remained high. In addition, Con A-stimulated spleen cells from acute DBA/2 mice produced approximately twice as much IL-10 and significantly more IL-4 than cells from B10.D2 mice. IL-4 secretion remained low by cells from chronic B10.D2 mice, but when using cells from chronic DBA/2 mice, levels continued to increase beyond the already high levels secreted by cells harvested during the acute phase. Proliferative responses to Con A stimulation by spleen cells from DBA/2 mice were significantly higher than those from B10.D2 mice in both the acute and chronic phases. These data suggest that enhanced responses in DBA/2 mice, which may be related to a higher parasite burden, a lack of down-regulation, and/or the onset of autoimmune phenomena, correlate with the more severe cardiomyopathy seen in pathopermissive mice.