Role of the CX3CR1 chmokine receptor and LFA-1 integrin in the differentiation and activation of CD8 T lymphocytes during Trypanosoma cruzi infection

• Grant number: 19/17994-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2019
• End date: May 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Ronnie Carvalho de Vasconcelos
• Grantee: Leonardo Moro Cariste
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated research grant: 18/15607-1 - Role of specific CD4+ and CD8+ T cells generated by different vaccination protocols against experimental Trypanosoma cruzi infection, AP.JP2

Abstract

CD8 + T lymphocytes play an important role in the control of infections by intracellular pathogens such as Trypanosoma cruzi, a causative agent of Chagas Disease. These lymphocytes control infection by the release of IFN-g and by the elimination of the target cells infected by direct cytotoxicity. To perform these functions, lymphocytes must migrate to infected tissues, establish stable contact with antigen-presenting cells, and be activated through the interaction of TCR with the MHC-peptide complex and costimulatory molecules. Chemokine and integrin molecules are essential for the migration of T lymphocytes to the sites of infection. In addition, the role of these molecules in the activation and differentiation of CD8 + T lymphocytes during viral and bacterial infections has now been reported. However, the role of these molecules during T. cruzi infection is unclear. Interestingly, CX3CR1 and CXCR3 chemokine molecules are highly expressed on the surface of CD8 + T lymphocytes during infection by intracellular pathogens, such as T. cruzi, and are important in the activation and differentiation of these cells. Studies indicate that chemokines and integrins are important in facilitating the encounter of these lymphocytes with the antigen-presenting cells in the lymph node, and consequently in the activation and subsequent differentiation of the lymphocytes. LFA-1 integrin also plays a role in the activation and differentiation of lymphocytes, since it is extremely important in establishing the contact of lymphocytes with antigen-presenting cells. However, there are still few works in the literature that describe exactly how this molecule interferes in the induction of memory cells. Our preliminary results demonstrated that blockade of CXCR3 and/or LFA-1 render mice of the C57BL/6 strain susceptible to T. cruzi infection. Further, we note that the chemokine receptor CX3CR1 is highly expressed in the CD8 + T cells of the infected animals. Therefore, the objective of this project is to evaluate the role of CXCR3 and CX3CR1 chemokines and LFA-1 integrin in the differentiation of memory effector cells and activation of CD8 + T lymphocytes during T. cruzi infection. Knowledge of the mechanisms involved in the induction of effector cells that will give rise to memory cells is extremely important for the generation of vaccine strategies. (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)

PONTES FERREIRA, CAMILA; MORO CARISTE, LEONARDO DE; HENRIQUE NORONHA, ISAU; FERNANDES DURSO, DANIELLE; LANNES-VIEIRA, JOSELI; RAMALHO BORTOLUCI, KARINA; ARAKI RIBEIRO, DANIEL; GOLENBOCK, DOUGLAS; GAZZINELLI, RICARDO TOSTES; VASCONCELOS, JOSE RONNIE CARVALHO DE. CXCR3 chemokine receptor contributes to specific CD8(+) T cell activation by pDC during infection with intracellular pathogens. PLoS Neglected Tropical Diseases, v. 14, n. 6, JUN 2020. (18/15607-1, 15/08814-2, 19/17994-5, 16/02840-4)