Regulation of the T1 or T2 immune response with the use of recombinant cytokines in mononuclear cells of dogs with Visceral Leishmaniasis

• Grant number: 17/10906-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2017
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Valéria Marçal Felix de Lima
• Grantee: Sidnei Ferro Costa
• Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The progression of Canine Visceral Leishmaniasis (CVL) is accompanied by asuppression of cellular immunity probably associated with the inhibition of a cellular response, characterized by a reduction in the number of T lymphocytes and production of the cytokine INF-gamma that suppresses the function of macrophages. Moreover, the PD1 molecule (Programed Cell Death 1) is highly expressed inleukocyte cells in CVL and induces inhibition of the proliferative antigen response and apoptosis of T cells. Cytokines associated with the cell immune response IL-2, IL-12 and INF-³ are highly expressed in different tissues of dogs with asymptomatic leishmaniasis, suggesting that cytokines play a role in disease resistance, while that the IL-10 cytokine associated with humoral response was correlated positively the absence or decrease of INF-³ production and increased parasite load on acute LVC. No studies have yet been performed to evaluate the appropriate conditions for differentiation of the cellular or the ability of the IL-2, IL-12, IL-7 and IL-15 cytokines was not evaluated either to promote lymphoproliferation in healthy and LV dogs. Therefore we will evaluate the combination of canine recombinant reagents IL-2, IL-12, IL-7 and IL-15 and / or soluble receptor of IL-10R (with antagonistic action) is capable to induce differentiation of T1 and T2-like effector T lymphocytes, promote the proliferation of specific antigen T cells and regulate the expression of negative costimulatory molecule PD-1.

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)

COSTA, SIDNEI FERRO; GOMES, VINICIUS OLIVEIRA; DOS SANTOS MACIEL, MARILENE OLIVEIRA; MELO, LARISSA MARTINS; VENTURIN, GABRIELA LOVIZUTTO; BRAGATO, JAQUELINE POLETO; REBECH, GABRIELA TORRES; SANTOS, CATIULE DE OLIVEIRA; NASCIMENTO DE OLIVEIRA, BARBARA MARIA; DE SA OLIVEIRA, GERALDO GILENO; et al. Combined in vitro IL-12 and IL-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis. PLoS Neglected Tropical Diseases, v. 14, n. 1, JAN 2020. (17/10906-8)

SANTOS, CATIULE DE OLIVEIRA; COSTA, SIDNEI FERRO; SOUZA, FABIANA SANTANA; FERREIRA MENDES, JESSICA MARIANE; MELO DE PINHEIRO, CRISTIANE GARBOGGINI; DE MAGALHAES MOREIRA, DIOGO RODRIGO; SILVA, LUCIANO KALABRIC; FELIX DE LIMA, VALERIA MARCAL; DE SA OLIVEIRA, GERALDO GILENO. Blocking IL-10 signaling with soluble IL-10 receptor restores in vitro specific lymphoproliferative response in dogs with leishmaniasis caused by Leishmania infantum. PLoS One, v. 16, n. 1, JAN 19 2021. (17/10906-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COSTA, Sidnei Ferro. Combined stimulation by IL-12 and IL-15 promotes cellular immune response in dogs with visceral leishmaniasis via IFN-y.. 2019. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária. Araçatuba Araçatuba.