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Role of mirRNA21 and miRNA 148 on immune regulation of splenic leukocytes in canine visceral leishmaniasis

Grant number: 18/17261-5
Support Opportunities:Regular Research Grants
Start date: November 01, 2018
End date: October 31, 2021
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Valéria Marçal Felix de Lima
Grantee:Valéria Marçal Felix de Lima
Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated researchers:Flavia Lombardi Lopes

Abstract

LVA Visceral leishmaniasis (LV) is a chronic and often fatal disease in man. According to the Secretary of Epidemiological Surveillance of the State of São Paulo, the disease is expanding with a high mortality rate, with the Araçatuba region concentrating a large number of cases in the state. Visceral Canine Leishmaniasis (LVC) is a serious public health problem because infected animals are powerful transmitters of the parasite to humans by the phlebotomain vector, and canine disease is more prevalent than the human disease and usually canine cases precede human cases. The dog is therefore an important target in the control measures. The progression of canine infection is accompanied by failure of cellular immunity with reduction of circulating lymphocytes and cytokines that suppress the function of macrophages. The function of the T cell in the induction of the cellular response is determinant for the elimination of the parasite inside the macrophages. Although immune suppression is already characterized, the determining factors are poorly understood. In the last decade studies have shown that the regulation of the effector function of macrophages and T cells seems to depend on miRNAs. There is much evidence of the role of miRNAs in regulating the expression of proteins that are critical for the development, function, and differentiation of various cellular types of the immune system. MiRNA 21 and miRNA 148a have increased expression in splenic leukocytes from dogs with VL and targets several proteins related to the immune response. Molecular tools will be used to increase or decrease miR21 and miR148a and the expression of the FAS, FASL, TNF-±, CD69, CCR7, IL-12 and TGF-beta,CD80 and iNOS proteins will be evaluated. Our results will improve our understanding of the pathogenesis of VL in the host, and as such, reveal new pathways that may be therapeutic targets. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
BRAGATO, JAQUELINE POLETO; REBECH, GABRIELA TORRES; DE FREITAS, JESSICA HENRIQUE; DOS SANTOS, MARILENE OLIVEIRA; COSTA, SIDNEI FERRO; EUGENIO, FLAVIA DE REZENDE; PATTO DOS SANTOS, PAULO SERGIO; FELIX DE LIMA, VALERIA MARCAL. miRNA-21 regulates CD69 and IL-10 expression in canine leishmaniasis. PLoS One, v. 17, n. 3, p. 15-pg., . (18/16239-6, 18/17261-5)
REBECH, GABRIELA TORRES; BRAGATO, JAQUELINE POLETO; COSTA, SIDNEI FERRO; DE FREITAS, JESSICA HENRIQUE; DOS SANTOS, MARILENE OLIVEIRA; SOARES, MATHEUS FUJIMURA; EUGENIO, FLAVIA DE REZENDE; DOS SANTOS, PAULO SERGIO PATTO; DE LIMA, VALERIA MARCAL FELIX. miR-148a regulation interferes in inflammatory cytokine and parasitic load in canine leishmaniasis. PLoS Neglected Tropical Diseases, v. 17, n. 1, p. 19-pg., . (18/17261-5, 18/16239-6, 21/07283-4, 19/04240-2)
DE FREITAS, JESSICA HENRIQUE; BRAGATO, JAQUELINE POLETO; REBECH, GABRIELA TORRES; COSTA, SIDNEI FERRO; DOS SANTOS, MARILENE OLIVEIRA; SOARES, MATHEUS FUJIMURA; EUGENIO, FLAVIA DE REZENDE; DOS SANTOS, PAULO SERGIO PATTO; DE LIMA, VALERIA MARCAL FELIX. MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis. FRONTIERS IN GENETICS, v. 14, p. 12-pg., . (18/17261-5, 21/07283-4)