| Grant number: | 08/09176-6 |
| Support type: | Research Grants - Young Investigators Grants |
| Duration: | April 01, 2009 - March 31, 2013 |
| Field of knowledge: | Biological Sciences - Immunology - Cellular Immunology |
| Principal Investigator: | Ronei Luciano Mamoni |
| Grantee: | Ronei Luciano Mamoni |
| Home Institution: | Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated scholarship(s): | 11/09883-7 - Characterization of the immunological response in human paracoccidioidomycosis,
BP.IC 09/05608-1 - Evaluation of the ability of diferentiation induction of Th7 cells by dendritic cells stimulated with Paracoccidoides brasiliensis antigens and the signaling mechanisms envolved., BP.DR 09/05377-0 - Evaluation of the participation of T helper-17 cells (Th17) in human paracoccidioidomycosis, BP.JP |
Abstract
Paracoccidioidomycosis (PCM), a deep mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis, can be classified in two main clinical forms: the adult form (AF) in which the disease affect primarily the lungs, skin and oral mucosa; and the juvenile form (JF) characterized by the involvement of the phagocytic-mononuclear system, presenting a faster evolution and worst prognosis. Individuals living in the endemic area of the disease can present the PCM-infection (PI), considered the resistance form of the PCM. Individuals of PI group present a preserved cellular immune response, increased production of IFN-g and low production of IL-10, IL-4 and IL-5. On the other hand, patients with active PCM present a variable response, since a preserved cellular immune response, with low production of antibodies and IFN-g in the unifocal form; until a depressed cellular immune response, with presence of great number of eosinophils, high production of antibodies (IgG4 and IgE), IL-4, IL-5, IL-10 and TGF-b in the JF or in the multifocal AF. These characteristics demonstrate that the immunological response of susceptibility or resistance to paracoccidioidomycosis is regulated by a balance between the Th1 and Th2 responses. Nevertheless, some characteristics are not explained by this balance, as the fact that patients with active disease present a great production of inflammatory mediators and IL-12p40, but do not produce IL-12p70 and IFN-g; as well as, the fact of the presence of an inflammatory infiltrate composed by a great number of neutrophils, which present diminished fungicidal activity. These characteristics can be indication of the participation of IL-17 producing cells (Th17), a recently described subpopulation of lymphocytes, in the disease. Therefore, the objective of this project is to evaluate the participation of IL-17 producing cells in human paracoccidioidomycosis, in local lesions, by the analysis of oral mucosa and lymph node biopsies, as well as, in peripheral blood. (AU)