miRNA-21 regulates CD69 and IL-10 expression in canine leishmaniasis

• Published in: PloS one 2022-03, Vol.17 (3), p.e0265192-e0265192
• Main Authors: Bragato, Jaqueline Poleto, Rebech, Gabriela Torres, Freitas, Jéssica Henrique de, Santos, Marilene Oliveira Dos, Costa, Sidnei Ferro, Eugênio, Flavia de Rezende, Santos, Paulo Sérgio Patto Dos, de Lima, Valéria Marçal Felix
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antigens; Biology and Life Sciences; Blood tests; CCR7 protein; CD69 antigen; Cell culture; Cell-mediated immunity; Committees; Cytokines; Diseases; Dog Diseases - parasitology; Dogs; Ethics; FasL protein; Gene expression; Genetic aspects; Immune response; Immune system; Infections; Interleukin 10; Interleukin 17; Interleukin-10 - genetics; Interleukin-10 - therapeutic use; Kala-azar; Leishmania infantum; Leishmaniasis - veterinary; Leishmaniasis, Visceral - drug therapy; Leishmaniasis, Visceral - genetics; Leishmaniasis, Visceral - veterinary; Leukocytes; Lymphocytes; Lymphocytes T; Macrophages; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - therapeutic use; miRNA; Parasites; Parasitic diseases; Public health; Receptors, CCR7; Research and Analysis Methods; Serology; Spleen; Surgery; Therapeutic targets; Transfection; Transmitters; Tumor necrosis factor-α; Vector-borne diseases; Vectors; Veterinary colleges; Veterinary medicine; Visceral leishmaniasis; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0265192

Visceral leishmaniasis in humans is a chronic and fatal disease if left untreated. Canine leishmaniasis (CanL) is a severe public health problem because infected animals are powerful transmitters of the parasite to humans via phlebotomine vectors. Therefore, dogs are an essential target for control measures. Progression of canine infection is accompanied by failure of cellular immunity with reduction of circulating lymphocytes and increased cytokines that suppress macrophage function. Studies showed that the regulation of the effector function of macrophages and T cells appears to depend on miRNAs; miRNA-21 (miR-21) shows increased expression in splenic leukocytes of dogs with CanL and targets genes related to the immune response. Mimics and inhibitors of miR-21 were used in vitro to transfect splenic leukocytes from dogs with CanL. After transfection, expression levels of the proteins FAS, FASL, CD69, CCR7, TNF-α, IL-17, IFN-γ, and IL-10 were measured. FAS, FASL, CD69, and CCR7 expression levels decreased in splenic leukocytes from dogs with CanL. The miR-21 mimic decreased CD69 expression in splenic leukocytes from CanL and healthy groups. The miR-21 inhibitor decreased IL-10 levels in culture supernatants from splenic leukocytes in the CanL group. These findings suggest that miR-21 alters the immune response in CanL; therefore, miR-21 could be used as a possible therapeutic target for CanL.