Evaluation of the role of T regulator and Th17 cells during experimental infection with Toxoplasma gondii

• Grant number: 09/13890-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2010
• End date: April 30, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Denise Morais da Fonseca
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 07/53940-0 - The regulatory T cells and TH17 in the immune response against infections, tumors and autoimmune diseases, AP.TEM
• Associated scholarship(s): 12/14669-7 - Dendritic cells and pattern recognition receptors in the activation and plasticity of T lymphocytes subpopulations during intestinal mucosal inflammation, BE.EP.PD

Abstract

The description of new T lymphocytes subtypes, besides Th1 and Th2 cells, conduced the immunologists to an intense review of previously proposed mechanisms to explain the immunological events associated to immune responses against pathogens and during autoimmune diseases, as well as the processes responsible for controlling these responses. In this context, the role of regulatory and Th17 cells has been evidenced, especially during the immune responses against pathogens, because of the antagonistic functions attributed to these lymphocytes subtypes. In addition, the Th17 cells are reciprocally related to Foxp3+ regulatory T cells, once the presence of TGF-b induces Foxp3 expression in lymphocytes, while IL-6 suppress regulatory T cells differentiation and, together with TGF-b, drives the ROR-gt expression and the consequent Th17 lymphocyte development. Besides these cytokines, environmental factors are also associated with the differentiation of these cell subtypes, as the retinoic acid and the interaction of pathogens products with receptors from innate immunity. These events are crucial to drive the response during infections, once the regulatory T cell activation causes the down-regulation of immune response and preservation of tissues. However, the regulatory cells activation leads to the pathogen persistence. On the other way, the Th17 cells are essential to sustain the microbicide mechanisms of immune cells, but when T17 cells are excessively recruited, they might cause tissue damage. The oral infection with Toxoplasma gondii induces a pathological response. In this disease, the balance between inflammation and regulation determines the evolution of the host pathology, because the protective immunity is associated with an inflammatory response, which might cause tissue damage to the host. Therefore, it is possible that regulatory and Th17 cells might be involved in the control or in the progression of this disease. For these reasons, the aim of this project is to evaluate the involvement of regulatory and Th17 cells on the susceptibility or resistance of distinct mice stains to experimental toxoplasmosis. (AU)