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Role of CX3CR1 chemokine receptor and the integrin LFA-1 in the differentiation and activation of CD8 + t lymphocytes during Trypanosoma cruzi infection

Grant number: 17/11499-7
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2017
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Jose Ronnie Carvalho de Vasconcelos
Grantee:Leonardo Moro Cariste
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
Associated research grant:12/22514-3 - Migration study of specific T cells generated by vaccination or Trypanosoma cruzi infection, AP.JP

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 infection through the release of IFN-g and the elimination of infected target cells 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 the 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 to facilitate the encounter of these lymphocytes with the antigen-presenting cells in the lymph node, and consequently, in the activation and subsequent differentiation of lymphocytes. LFA-1 integrin also plays a role in the activation and differentiation of lymphocytes, since it is extremely important in establishing 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. Furthermore, we observed 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. The knowledge of the mechanisms involved with the induction of effector cells that will give rise to the memory cells is of extreme importance 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)
FERREIRA, CAMILA PONTES; CARISTE, LEONARDO MORO; MORASCHI, BARBARA FERRI; ZANETTI, BIANCA FERRARINI; HAN, SANG WON; RIBEIRO, DANIEL ARAKI; MACHADO, ALEXANDRE VIEIRA; LANNES-VIEIRA, JOSELI; GAZZINELLI, RICARDO TOSTES; CARVALHO VASCONCELOS, JOSE RONNIE. CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge. PLoS Neglected Tropical Diseases, v. 13, n. 7 JUL 2019. Web of Science Citations: 0.
FERREIRA, CAMILA PONTES; CARISTE, LEONARDO MORO; VIRGILIO, FERNANDO DOS SANTOS; MORASCHI, BARBARA FERRI; MONTEIRO, CAROLINE BRANDAO; VIEIRA MACHADO, ALEXANDRE M.; GAZZINELLI, RICARDO TOSTES; BRUNA-ROMERO, OSCAR; MENIN RUIZ, PEDRO LUIZ; RIBEIRO, DANIEL ARAKI; LANNES-VIEIRA, JOSELI; LOPES, MARCELA DE FREITAS; RODRIGUES, MAURICIO MARTINS; CARVALHO DE VASCONCELOS, JOSE RONNIE. LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection. FRONTIERS IN IMMUNOLOGY, v. 8, OCT 13 2017. Web of Science Citations: 3.

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