Department of Animal Clinic, Surgery and Reproduction, São Paulo State University, School of Veterinary Medicine, Araçatuba, São Paulo, Brazil.
PLoS One. 2022 Mar 24;17(3):e0265192. doi: 10.1371/journal.pone.0265192. eCollection 2022.
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.
内脏利什曼病如果不治疗，在人类中是一种慢性和致命的疾病。犬利什曼病（CanL）是一个严重的公共卫生问题，因为受感染的动物通过白蛉媒介向人类传播寄生虫的能力很强。因此，狗是控制措施的重要目标。犬感染的进展伴随着细胞免疫的失败，循环淋巴细胞减少，细胞因子增加，抑制巨噬细胞功能。研究表明，巨噬细胞和 T 细胞效应功能的调节似乎依赖于 microRNA；microRNA-21（miR-21）在患有 CanL 的犬脾白细胞中表达增加，并靶向与免疫反应相关的基因。miR-21 的模拟物和抑制剂在体外用于转染患有 CanL 的犬的脾白细胞。转染后，测量 FAS、FASL、CD69、CCR7、TNF-α、IL-17、IFN-γ 和 IL-10 蛋白的表达水平。患有 CanL 的犬脾白细胞中的 FAS、FASL、CD69 和 CCR7 表达水平降低。miR-21 模拟物降低了 CanL 和健康组脾白细胞中的 CD69 表达。miR-21 抑制剂降低了 CanL 组脾白细胞培养上清液中的 IL-10 水平。这些发现表明，miR-21 改变了 CanL 中的免疫反应；因此，miR-21 可以用作 CanL 的潜在治疗靶标。
