MiRNA 21 in the regulation of immune response in Canine Visceral Leishmaniasis

• Grant number: 18/16239-6
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2019
• Effective date (End): August 31, 2021
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal researcher: Valéria Marçal Felix de Lima
• Grantee: Jaqueline Poleto Bragato
• Home Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Visceral Leishmaniasis (VL) in humans is a chronic and often fatal disease if left untreated. 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. Canine Visceral Leishmaniasis (CVL) is a serious public health problem because infected animals are powerful transmitters of the parasite to humans by phlebotomain vector, canine disease is more prevalent than 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 T cell in the induction of 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 are much evidences 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 has increased expression in splenic leukocytes of dogs with VL and targets several proteins related to the immune response. Molecular tools will be used to increase or decrease miR21 and the expression of FAS, FASL, TNF-a, CD69 and CCR7 proteins will be evaluated. Our results will improve understanding of the pathogenesis of VL in the host, and as such, reveal new pathways that may be therapeutic targets. (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)

MELO, LARISSA MARTINS; BRAGATO, JAQUELINE POLETO; VENTURIN, GABRIELA LOVIZUTTO; REBECH, GABRIELA TORRES; COSTA, SIDNEI FERRO; GARCIA, LEANDRO ENCARNACAO; LOPES, FLAVIA LOMBARDI; EUGENIO, FLAVIA DE REZENDE; PATTO DOS SANTOS, PAULO SERGIO; FELIX DE LIMA, VALERIA MARCAL. Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes. PLoS One, v. 14, n. 12 DEC 11 2019. Web of Science Citations: 0.