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Modulation of T lymphocytes differentiation in infections by Protozoa, Fungi and Bacteria

Grant number: 12/14524-9
Support type:Research Projects - Thematic Grants
Duration: April 01, 2013 - March 31, 2016
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:João Santana da Silva
Grantee:João Santana da Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Vânia Luiza Deperon Bonato
Assoc. researchers: Amélia Maria Ribeiro de Jesus ; Cristina Ribeiro de Barros Cardoso ; Daniela Carlos Sartori ; Dario Simões Zamboni ; Fernando de Queiroz Cunha ; Marcos Antonio Rossi ; Niels Olsen Saraiva Câmara ; Roque Pacheco de Almeida ; Thiago Mattar Cunha ; Vanessa Carregaro Pereira
Associated scholarship(s):15/21605-3 - The role of NLRC4 inflammasome in the control of Paracoccidioides Brasiliensis, BP.MS
14/14859-6 - Role of NFAT during experimental infection induced by T. gondii, BP.IC
13/21295-9 - Role of canonical and non-canonical inflammasome in modulating the innate immune response during infection with Paracoccidioides brasiliensis, BP.DD
12/20786-6 - Molecular mechanisms involved in dendritic cell differentiation and CD4+ t cells polarization that confer resistance to viral infection, BP.PD
13/08313-8 - Characterization of the role of Interleukin-27 (IL-27) during Leishmania infantum infection, BP.MS

Abstract

This project is based on two distinct goals. The first one is to strengthen our research group. The multidisciplinary nature and its technical and scientific approaches result in the congregation of a large group of scientists, which already interact regularly. The project works with a strong graduate program, being that the maintenance of the animal roons, the flow cytometry, and general support room is essential for us. Financial support will maintain and improve the group's working conditions, therefore strengthening it and increasing the amount and quality of scientific knowledge that it generates, as well as the number and quality of scientists formed by the graduate program. The scientific goal is to determine the role of innate receptors, transcription factors, of the cytokines IL-6, IL-22 and IL-23 in the helper T cells polarization during the infection with T. cruzi, L. infantum, T. gondii, Micobacterium tuberculosis and Paracoccidioides brasiliensis. The T cells orchestrate the defense against invasions and the resulting immune response may lead to elimination of parasites or maintenance thereof, as a latent infection. While infections in some patients appear to be adequately controlled, as the hosts are asymptomatic, other develops symptoms, with injuries ranging from mild to very serious, both during acute and chronic phase. Using various experimental models, experiments in vivo and in vitro, we will focus on the regulation of lymphocyte activation, particularly Th9, Th17, Th22 and Treg in order to understand how is the control of such immune response. The influence of innate immunity in the determination of such responses is a main focus of this project. The goal is to understand the mechanisms responsible for the defense, resulting in latent infection and that can cause injuries and diseases, opening new possibilities for immunointervention. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Key substance for treatment of visceral leishmaniasis identified 

Scientific publications (13)
(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)
SACRAMENTO, LAIS AMORIM; BENEVIDES, LUCIANA; MARUYAMA, SANDRA REGINA; TAVARES, LUCAS; FUKUTANI, KIYOSHI FERREIRA; FRANCOZO, MARCELA; SPARWASSER, TIM; CUNHA, FERNANDO QUEIROZ; ALMEIDA, ROQUE PACHECO; DA SILVA, JOAO SANTANA; CARREGARO, VANESSA. TLR4 abrogates the Th1 immune response through IRF1 and IFN-beta to prevent immunopathology during L. infantum infection. PLOS PATHOGENS, v. 16, n. 3 MAR 2020. Web of Science Citations: 0.
KETELUT-CARNEIRO, NATALIA; SILVA SOUZA, CAMILA OLIVEIRA; BENEVIDES, LUCIANA; GARDINASSI, LUIZ GUSTAVO; SILVA, MARIA CLAUDIA; TAVARES, LUCAS ALVES; ZAMBONI, DARIO SIMOES; SILVA, JOAO SANTANA. Caspase-11-dependent IL-1 alpha release boosts Th17 immunity against Paracoccidioides brasiliensis. PLOS PATHOGENS, v. 15, n. 8 AUG 2019. Web of Science Citations: 1.
SILVA, MARIA C.; DAVOLI-FERREIRA, MARCELA; MEDINA, TIAGO S.; SESTI-COSTA, RENATA; SILVA, GRACE K.; LOPES, CARLA D.; CARDOZO, LUCAS E.; GAVA, FABIO N.; LYRONI, KONSTANTINA; DIAS, FABRICIO C.; FRADE, AMANDA F.; BARON, MONIQUE; NAKAYA, HELDER I.; FIGUEIREDO, FLORENCIO; ALVES-FILHO, JOSE C.; CUNHA, FERNANDO Q.; TSATSANIS, CHRISTOS; CHEVILLARD, CHRISTOPHE; CUNHA-NETO, EDECIO; HIRSCH, EMILIO; SILVA, JOAO S.; CUNHA, THIAGO M. Canonical PI3K gamma signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis. NATURE COMMUNICATIONS, v. 9, APR 17 2018. Web of Science Citations: 6.
MEDINA, TIAGO SILVA; OLIVEIRA, GABRIELA GONCALVES; SILVA, MARIA CLAUDIA; DAVID, BRUNA ARAUJO; SILVA, GRACE KELLY; FONSECA, DENISE MORAIS; SESTI-COSTA, RENATA; FRADE, AMANDA FARAGE; BARON, MONIQUE ANDRADE; IANNI, BARBARA; PEREIRA, ALEXANDRE COSTA; CHEVILLARD, CHRISTOPHE; CUNHA-NETO, EDECIO; MARIN-NETO, JOSE ANTONIO; SILVA, JOAO SANTANA. Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-gamma-Driven Inflammation. FRONTIERS IN IMMUNOLOGY, v. 8, SEP 26 2017. Web of Science Citations: 8.
KETELUT-CARNEIRO, NATALIA; GHOSH, SREYA; LEVITZ, STUART M.; FITZGERALD, KATHERINE A.; DA SILVA, JOAO SANTANA. A Dectin-1-Caspase-8 Pathway Licenses Canonical Caspase-1 Inflammasome Activation and Interleukin-1 beta Release in Response to a Pathogenic Fungus. Journal of Infectious Diseases, v. 217, n. 2, p. 329-339, JAN 15 2017. Web of Science Citations: 4.
QUIRINO, GUSTAVO F. S.; NASCIMENTO, MANUELA S. L.; DAVOLI-FERREIRA, MARCELA; SACRAMENTO, LAIS A.; LIMA, MIKHAEL H. F.; ALMEIDA, ROQUE P.; CARREGARO, VANESSA; SILVA, JOAO SANTANA. Interleukin-27 (IL-27) Mediates Susceptibility to Visceral Leishmaniasis by Suppressing the IL-17-Neutrophil Response. Infection and Immunity, v. 84, n. 8, p. 2289-2298, AUG 2016. Web of Science Citations: 12.
BERTOLINI, THAIS BARBOZA; DE SOUZA, ALEXANDRE IGNACIO; GEMBRE, ANA FLAVIA; PINEROS, ANNIE ROCIO; PRADO, RAFAEL DE QUEIROZ; SILVA, JOAO SANTANA; ZAMBELLI RAMALHO, LEANDRA NAIRA; DEPERON BONATO, VANIA LUIZA. Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis-infected hosts. Immunology, v. 148, n. 1, p. 102-113, MAY 2016. Web of Science Citations: 7.
SACRAMENTO, LAIS; TREVELIN, SILVIA C.; NASCIMENTO, MANUELA S.; LIMA-JUNIOR, DJALMA S.; COSTA, DIEGO L.; ALMEIDA, ROQUE P.; CUNHA, FERNANDO Q.; SILVA, JOAO S.; CARREGARO, VANESSA. Toll-Like Receptor 9 Signaling in Dendritic Cells Regulates Neutrophil Recruitment to Inflammatory Foci following Leishmania infantum Infection. Infection and Immunity, v. 83, n. 12, p. 4604-4616, DEC 2015. Web of Science Citations: 10.
BENEVIDES, LUCIANA; DA FONSECA, DENISE MORAIS; DONATE, PAULA BARBIM; TIEZZI, DANIEL GUIMARAES; DE CARVALHO, DANIEL D.; DE ANDRADE, JURANDYR M.; MARTINS, GISLAINE A.; SILVA, JOAO S. IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment. Cancer Research, v. 75, n. 18, p. 3788-3799, SEP 15 2015. Web of Science Citations: 50.
KETELUT-CARNEIRO, NATALIA; SILVA, GRACE KELLY; ROCHA, FERNANDA AGOSTINI; MILANEZI, CRISTIANE MARIA; CAVALCANTI-NETO, FLORENCIO FIGUEIREDO; ZAMBONI, DARIO SIMOES; SILVA, JOAO SANTANA. IL-18 Triggered by the Nlrp3 Inflammasome Induces Host Innate Resistance in a Pulmonary Model of Fungal Infection. JOURNAL OF IMMUNOLOGY, v. 194, n. 9, p. 4507-4517, MAY 1 2015. Web of Science Citations: 31.
LIMA NASCIMENTO, MANUELA SALES; CARREGARO, VANESSA; LIMA-JUNIOR, DJALMA SOUZA; COSTA, DIEGO LUIS; RYFFEL, BERNHARD; DUTHIE, MALCOLM S.; DE JESUS, AMELIA; DE ALMEIDA, ROQUE PACHECO; DA SILVA, JOAO SANTANA. Interleukin 17A Acts Synergistically With Interferon gamma to Promote Protection Against Leishmania infantum Infection. Journal of Infectious Diseases, v. 211, n. 6, p. 1015-1026, MAR 15 2015. Web of Science Citations: 42.
BONFA, GIULIANO; BENEVIDES, LUCIANA; SOUZA, MARIA DO CARMO; FONSECA, DENISE MORAIS; PATRIARCA MINEO, TIAGO WILSON; ROSSI, MARCOS ANTONIO; SILVA, NEIDE MARIA; SILVA, JOAO SANTANA; DE BARROS CARDOSO, CRISTINA RIBEIRO. CCR5 Controls Immune and Metabolic Functions during Toxoplasma gondii Infection. PLoS One, v. 9, n. 8 AUG 13 2014. Web of Science Citations: 8.
SACRAMENTO, LAIS AMORIM; CUNHA, FERNANDO Q.; DE ALMEIDA, ROQUE PACHECO; DA SILVA, JOAO SANTANA; CARREGARO, VANESSA. Protective Role of 5-Lipoxigenase during Leishmania infantum Infection Is Associated with Th17 Subset. BIOMED RESEARCH INTERNATIONAL, 2014. Web of Science Citations: 12.

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