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Role of integrin receptors and chemokines in the migration of specific CD8+ T cells generated by genetic immunization with ASP -2 Trypanosoma cruzi

Grant number: 15/08814-2
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): December 01, 2015
Effective date (End): September 30, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Jose Ronnie Carvalho de Vasconcelos
Grantee:Camila Pontes Ferreira
Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:12/22514-3 - Migration study of specific T cells generated by vaccination or Trypanosoma cruzi infection, AP.JP
Associated scholarship(s):17/21314-4 - Role of the CXCR3 chemokine receptor in the differentiation,migration, activation and functionality of t lymphocytes during Trypanosoma Cruzi infection, BE.EP.DD

Abstract

Trypanosoma cruzi is the causative agent of Chagas disease, a neglected disease that is endemic in South and Central America, affecting approximately 10 million. CD8 + T cells play a key role in protective immunity against intracellular pathogens such as T. cruzi. The heterologous prime-boost immunization consists of a booster dose with two different genetic vectors carrying the same gene, one important strategy to generate CD8 + T cells and protection against experimental infection with T. cruzi. This protection is dependent lymphocyte recirculation, since treatment with FTY720 drug that leads to the retention of specific CD8 + T cells in the lymph node, it vaccinated mice susceptible to infection. The recirculation is accomplished by molecules of chemokines and integrins, both of which mediate inflammation through recruitment and activation of CD8 + T cells and other leukocytes in several models of inflammatory diseases. In a recent study demonstrated that treatment with the monoclonal anti-LFA-1 (lymphocyte associated antigen 1 function) in A/Sn mice immunized and infected reversed the protective immune response elicited by the immunization after systemic challenge with the parasite. This treatment did not affect the frequency of CD8 + T cells specific and not the effector function of these lymphocytes in the production of cytokines such as IFNg and TNFa. The same reversal was observed after treatment with anti-CXCR3 monoclonal antibody in A/Sn mice immunized and infected, and also did not observe any reduction in the frequency and the effector function specific CD8 + T cells. The results so far have shown the importance of these molecules in our vaccination and infection model, so the general objective of this Direct PhD proposal (DD) is continuing the studies obtained in the master, but use new experimental approach to elucidate the mechanisms and functions of these molecules. (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.
ERSCHING, JONATAN; VASCONCELOS, JOSE R.; FERREIRA, CAMILA P.; CAETANO, BRAULIA C.; MACHADO, ALEXANDRE V.; BRUNA-ROMERO, OSCAR; BARON, MONIQUE A.; FERREIRA, LUDMILA R. P.; CUNHA-NETO, EDECIO; ROCK, KENNETH L.; GAZZINELLI, RICARDO T.; RODRIGUES, MAURCIO M. The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8(+) T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi. PLOS PATHOGENS, v. 12, n. 4 APR 2016. Web of Science Citations: 5.

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