Tesis doctoral de Cristina Sanoja Wasylkowski
Chagas disease is caused by infection with the protozoan haemoflagellate trypanosoma cruzi and there are 8 million infected people in latin america. A feature of the acute phase of the infection is the proliferation of circulating and intracellular parasites; these can invade most of the tissues, mainly the cardiac fibers. Scarce number of parasites is found during the chronic phase and cardiac hypertrophy, flabby heart and other cardiomiopathies can be detected. However, some chagasic patients never develop clinical manifestation during the chronic phase. There is not a clear picture of the cellular and molecular characteristics of the pathogenesis of t. Cruzi infection. Some authors have proposed that the cardiac chronic pathogenesis depends of a constant and very low systemic infection, associated with an adverse immune reaction, in such a way that the persistence of parasites and immunological mechanisms, closely related, are involved in the long term myocardial aggression. During the parasitic infection, the immune regulation can emerge as an attenuating effect of the host immune response against the parasite and/or could be actively induce by the parasite itself as a survival strategy. Our main objective was to determine the possible role of the t regulatory cells and th17 in the modulation of the experimental chagas pathology during the acute and chronic phase of infection. Different experimental models were established to evaluate the molecular and immunological events responsible by the cardiac pathogenesis in chagas disease. As a result of this investigation, a high gen expression of inflammatory myeloid and lymphoid cellular populations (cd4, cd8, b220, cd68, cd11b and cd11c) and t cell regulatory markers (foxp3, fr4, ctla¿4 and gitr) were detected in the cardiac tissue of the less susceptible c57bl/6 strain of mice, but not in the more susceptible balb/c strain. these results were confirmed by a flow cytometry analysis of the cardiac inflammatory infiltrate. On the contrary, we have not found a clear th17 response in our working models, suggesting that any association between th17 cells and susceptibility to infection do not seem to exist. Our results also suggest that the regulatory t cells could play an immunosuppressor role during the acute phase of the disease but not in the chronic phase. this regulatory t cell response should be beneficial to the host, increasing the survival time of the mice, decreasing the circulating and cardiac parasitic load and controlling the inflammation of the target organ, the heart. xxv
Datos académicos de la tesis doctoral «Respuesta inmunoreguladora y su relación con la inmunopatología cardiaca en la infección por trypanosoma cruzi.«
- Título de la tesis: Respuesta inmunoreguladora y su relación con la inmunopatología cardiaca en la infección por trypanosoma cruzi.
- Autor: Cristina Sanoja Wasylkowski
- Universidad: Autónoma de Madrid
- Fecha de lectura de la tesis: 07/09/2010
Dirección y tribunal
- Director de la tesis
- Nuria Girones Pujol
- Tribunal
- Presidente del tribunal: lisardo Boscá gomar
- José Alberto García sanz (vocal)
- Francisco Javier Moreno nuncio (vocal)
- sara Ballester jareño (vocal)