Role of the CXCR3 chemokine receptor in the differentiation, migration, activation and functionality of T lymphocytes during Trypanosoma cruzi infection

• Grant number: 17/21314-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 29, 2018
• End date: January 28, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Ronnie Carvalho de Vasconcelos
• Grantee: Camila Pontes Ferreira
• Supervisor: Ricardo Tostes Gazzinelli
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Massachusetts Medical School (UMMS), United States
• Associated to the scholarship: 15/08814-2 - Role of integrin receptors and chemokines in the migration of specific CD8+ T cells generated by genetic immunization with ASP -2 Trypanosoma cruzi, BP.DD

Abstract

CD8+ T lymphocytes play an important role in the control of infections by intracellular pathogens such as Trypanosoma cruzi, the causative agent of Chagas disease. These lymphocytes control the infection by releasing IFN-g or by direct cytotoxicity against infected target cells. To perform such functions, the lymphocytes migrate into the infected tissues, establish a stable contact with antigen-presenting cells, and are activated through the interaction between TCR and the MHC-peptide complex and costimulatory molecules. Chemokine molecules are essential to T lymphocytes migration into the sites of infection. Currently, the role of these molecules in the activation and differentiation of CD8+ T lymphocytes during viral and bacterial infections has been reported. However, their role during T. cruzi infection is unclear. Interestingly, CXCR3 chemokine molecule is highly expressed on the surface of CD8+ T lymphocytes during infection by intracellular pathogens such as T. cruzi. Studies indicate that chemokines guide these lymphocytes to the antigen-presenting cells in the lymph nodes, and consequently, help with activation and differentiation of lymphocytes. However, there are still few studies in the literature describing exactly how this molecule interferes with the activation and function of these cells. Our preliminary results demonstrated that CXCR3 blockade makes the C57BL/6 mice susceptible to T. cruzi infection. Therefore, the objective of this project is to evaluate the role of CXCR3 chemokine in the differentiation and functionality of T lymphocytes effector during T. cruzi infection. Knowing the mechanisms involved in the induction of effector cells that will give rise to functional memory cells is fundamental to the development of vaccine strategies. (AU)