| Grant number: | 17/01390-8 |
| Support Opportunities: | Regular Research Grants |
| Start date: | April 01, 2017 |
| End date: | March 31, 2019 |
| Field of knowledge: | Biological Sciences - Immunology - Cellular Immunology |
| Principal Investigator: | Ademilson Panunto-Castelo |
| Grantee: | Ademilson Panunto-Castelo |
| Host Institution: | Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
Abstract
Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungus Paracoccidioides brasiliensis or P. lutzii. The disease is autochthonous in Latin America, and the highest number of cases occur in Brazil. The disease manifests mainly as a progressive pulmonary infection that is characterized by a chronic granulomatous inflammation and tissue fibrosis. Depending on host and fungal factors, PCM can range from asymptomatic infection to severe disseminated disease. The response of the host to the fungus is dependent on the cellular immune response. Protection is related to a preponderance of the type 1 helper T lymphocytes (Th1), with production of interferon (IFN-) ³ and tumor necrosis factor (TNF-) ±, while the Th2 response, with production of interleukin (IL-) 4, IL-5, IL-10, makes it impossible to control fungal growth, causing active disease and dissemination of the fungus by the organism. Stress proteins (Hsp) are molecules that play a number of physiological roles within the cell, among them the correct folding process of newly synthesized proteins. Thus, when cells are subjected to stressor events, for example, thermal stress, infection, radiation, there is an increase in the production of these Hsp. Although the exact location of Hsp60 in Paracoccidioides spp. has not yet been determined, it is known that in mammals it is located within the mitochondria. When released by mammalian cells, Hsp60 is recognized by the immune system as a sign of cellular injury, which leads to the release of inflammatory mediators, with the presentation of these molecules by the antigen-presenting cells. Hsp60 appears to be important in the course of PCM, since sera from patients infected with Paracoccidioides spp. recognize this protein. Recently, our group showed that treatment of P. brasiliensis-infected mice with Hsp60 from that fungus induced increased fungal load and inflammation. In order to evaluate whether another way of presenting Hsp60 to the immune system could alter the response and be beneficial in the experimental PCM, in this study we will look for another form of induction of immune response against Hsp60, that is, the use of vaccine plasmid cloned with the Hsp60 gene from P. brasiliensis (pVAX1-tHsp60). To do so, mice will be infected with P. brasiliensis yeasts and, on day 20 after infection, they wiil be treated with pVAX1-tHsp60. To verify if the treatments were beneficial, test animals and controls will be analyzed for fungal load, inflammatory conditions and production of cytokines. (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |