Induction of miR 21 impairs the anti-Leishmania response through inhibition of IL-12 in canine splenic leukocytes

Author(s)

Melo, Larissa Martins ^[1] ; Bragato, Jaqueline Poleto ^[1] ; Venturin, Gabriela Lovizutto ^[1] ; Rebech, Gabriela Torres ^[1] ; Costa, Sidnei Ferro ^[1] ; Garcia, Leandro Encarnacao ^[2] ; Lopes, Flavia Lombardi ^[2] ; Eugenio, Flavia de Rezende ^[1] ; Patto dos Santos, Paulo Sergio ^[1] ; Felix de Lima, Valeria Marcal ^[1]

Affiliation

^[1] Sao Paulo State Univ Unesp, Sch Vet Med, Dept Anim Clin Surg & Reprod, Sao Paulo - Brazil

^[2] Sao Paulo State Univ Unesp, Sch Vet Med, Dept Prod & Anim Hlth, Aracatuba, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 14, n. 12 DEC 11 2019.
• Web of Science Citations: 0

Abstract

Visceral Leishmaniasis is a chronic zoonosis and, if left untreated, can be fatal. Infected dogs have decreased cellular immunity (Th1) and develop a potent humoral response (Th2), which is not effective for elimination of the protozoan. Immune response can be modulated by microRNAs (miRNAs), however, characterization of miRNAs and their possible regulatory role in the spleen of infected dogs have not been done. We evaluated miRNA expression in splenic leukocytes (SL) from dogs naturally infected with Leishmania infantum and developing leishmaniasis (CanL; n = 8) compared to healthy dogs (n = 4). Microarray analysis showed increased expression of miR 21, miR 148a, miR 7 and miR 615, and down-regulation of miR 150, miR 125a and miR 125b. Real-time PCR validated the differential expression of miR 21, miR 148a and miR 615. Further, decrease of miR 21 in SL, by means of transfection with a miR 21 inhibitor, increased the IL-12 cytokine and the T-bet/GATA-3 ratio, and decreased parasite load on SL of dogs with CanL. Taken together, these findings suggest that L. infantum infection alters splenic expression of miRNAs and that miR 21 interferes in the cellular immune response of L. infantum-infected dogs, placing this miRNA as a possible therapeutic target in CanL. (AU)

• FAPESP's process: 18/16239-6 - MiRNA 21 in the regulation of immune response in Canine Visceral Leishmaniasis
• Grantee: Jaqueline Poleto Bragato
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/16972-7 - The role of miRNA in Leishmania infantum infection in mononuclear cells and spleen leukocytes from peripheral blood of dog
• Grantee: Valéria Marçal Felix de Lima
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/16101-6 - The role of miRNAs in mononuclear cells infection of peripheral blood and spleen leukocytes the dog by Leishmania infantum
• Grantee: Larissa Martins Melo
• Support Opportunities: Scholarships in Brazil - Doctorate