Dendritic cells and pattern recognition receptors in the activation and plasticity of T lymphocytes subpopulations during intestinal mucosal inflammation

• Grant number: 12/14669-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 19, 2012
• End date: November 18, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Denise Morais da Fonseca
• Supervisor: Yasmine Belkaid
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: National Institutes of Health, Bethesda (NIH), United States
• Associated to the scholarship: 09/13890-9 - Evaluation of the role of T regulator and Th17 cells during experimental infection with Toxoplasma gondii, BP.PD

Abstract

The impairment of mechanisms involved in the regulation of immune responses in sites of high antigenic exposure, such as the intestinal mucosa, leads to the development of chronic inflammatory bowel diseases (IBD). The pathogenesis of IBDs is closely related to the breakdown of tolerance to intestinal microflora, an event that also occurs after infection with Toxoplasma gondii. This infection is a classic example in which a fine balance between activation/regulation of the immune system is necessary to promote the parasite clearance, to control the of the intestinal microbiota proliferation, without damaging the host tissues. The oral infection of mice with T. gondii causes the development of an intense inflammatory bowel disease that shares characteristic of inflammatory bowel disease in humans and may result in early death of susceptible hosts. The initial postdoctoral project developed (linked to this proposal) was aimed to determine the role of regulatory T cells (Treg) and Th17 cells in the control of intestinal inflammation induced by T. gondii in resistant and susceptible mice. In this study, we showed that the host genetic background determines the pattern of the adaptive immune response against the parasite, which in turn defines the course of the disease. We found that maintaining the number and the suppressive function of Treg cells, as well as the proper activation of Th17 and Th22 lymphocytes are essential for resistance against the disease. Although much is known about the influence of the cells from adaptive immune system in this process, it is still necessary to determine how the cells of innate immunity (via pattern recognition receptors) regulate the differentiation and the induction of plasticity of Treg, Th17 and Th22 lymphocytes and whether such regulation occurs differentially between resistant and susceptible mice strains. To achieve this goal, we propose to develop part of this project in a laboratory abroad, where we will rely on the expertise of researchers and the infrastructure necessary for development work, being able to expand our network of collaboration with researchers abroad. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA FONSECA, DENISE MORAIS; HAND, TIMOTHY W.; HAN, SEONG-JI; GERNER, MICHAEL Y.; ZARETSKY, ARIELLE GLATMAN; BYRD, ALLYSON L.; HARRISON, OLIVER J.; ORTIZ, ALEXANDRA M.; QUINONES, MARIAM; TRINCHIERI, GIORGIO; et al. Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity. Cell, v. 163, n. 2, p. 354-366, OCT 8 2015. (12/14669-7)