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


Autoři: Larissa Martins Melo aff001;  Jaqueline Poleto Bragato aff001;  Gabriela Lovizutto Venturin aff001;  Gabriela Torres Rebech aff001;  Sidnei Ferro Costa aff001;  Leandro Encarnação Garcia aff002;  Flavia Lombardi Lopes aff002;  Flávia de Rezende Eugênio aff001;  Paulo Sérgio Patto dos Santos aff001;  Valéria Marçal Felix de Lima aff001
Působiště autorů: Department of Animal Clinic, Surgery and Reproduction, São Paulo State University (Unesp), School of Veterinary Medicine, Araçatuba,São Paulo, Brazil aff001;  Department of Production and Animal Health, São Paulo State University (Unesp), School of Veterinary Medicine, Araçatuba, São Paulo, Brazil aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226192

Souhrn

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 downregulation 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.

Klíčová slova:

Dogs – Immune response – Macrophages – Microarrays – MicroRNAs – Signaling networks – Spleen – Transfection


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