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| Author(s): |
Thiago Alves da Costa
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2016-04-10 |
| Examining board members: |
Liana Maria Cardoso Verinaud;
Vânia Nieto Brito de Souza;
James Venturini;
Alessandro dos Santos Farias;
Elaine Conceição de Oliveira
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| Advisor: | Liana Maria Cardoso Verinaud |
| Abstract | |
The thymus is a primary lymphoid organ responsible for the maturation and development of T lymphocytes, to do this the thymic microenvironment needs to be preserved. Despite its importance, thymic involution occurs both in physiological conditions, as in aging, and in pathological conditions as seen in infections. Studies from our group have shown that experimental infection with Paracoccidioides brasiliensis, the causal agent of paracoccidioidomycosis, the most prevalent systemic mycosis on South and Central America, induces thymic atrophy. Here we investigated the participation of cell death mechanisms and inflammatory pathways on the thymic involution seen in P. brasiliensis experimentally infected mice. We observed marked cell loss on the thymus of those animals, in both thymic epithelial cells subpopulations and thymocytes subpopulations. This cell loss is due to the increase in apoptosis rates of these cells. The participation of intrathymic inflammatory mediators was observed in this process, with increased production of pro-inflammatory cytokines, highlighting IL-1? at the early stage of infection and IFN-? and TNF-? in the late phase. In addition, we observed intrathymic activation of the inflammasome NLRP3, a macromolecular complex involved in the activation of inflammatory caspases. Collectively, our data show that the pathogen remains viable and is able to multiply in the thymic microenvironment, causing molecular imbalance that affects the cells present in the stroma, such alterations compromises thymic function leading to premature egress at the early stage of infection and reduction of thymic export on the late phase. We believe that these results can contribute to a better understanding of peripheral immunosuppersion observed in clinical paracoccidioidomycosis (AU) | |
| FAPESP's process: | 12/22131-7 - Inflammation and cell death in thymic demise induced by Paracoccidioides brasiliensis |
| Grantee: | Thiago Alves da Costa |
| Support Opportunities: | Scholarships in Brazil - Doctorate |