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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 14, n. 12 DEC 11 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/16239-6 - MiRNA 21 na regulação da reposta imunológica na Leishmaniose Visceral Canina
• Beneficiário: Jaqueline Poleto Bragato
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/16972-7 - O papel dos miRNA na infecção de células mononucleares de sangue e baço de cão por Leishmania infantum
• Beneficiário: Valéria Marçal Felix de Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/16101-6 - O papel dos miRNAs na infecção de células mononucleares de sangue periférico e de leucócitos esplênicos de cão por Leishmania infantum
• Beneficiário: Larissa Martins Melo
• Modalidade de apoio: Bolsas no Brasil - Doutorado