Department of Clinic, Surgery and Animal Reproduction, Laboratory of Cellular Immunology, School of Veterinary Science of the São Paulo State University (Faculdade de Medicina Veterinária da Universidade Estadual Paulista "Júlio de Mesquita Filho", FMVA/UNESP), Rua Clóvis Pestana, 793, Araçatuba, São Paulo 16050-680, Brazil.
Vet Parasitol. 2013 Nov 8;197(3-4):470-6. doi: 10.1016/j.vetpar.2013.07.012. Epub 2013 Jul 19.
Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion.
感染的狗是内脏利什曼病（VL）的利什曼原虫（Leishmania chagasi）的城市储主。狗在这种疾病的过程中表现出免疫抑制，淋巴细胞凋亡参与了这个过程。为了研究凋亡以及外周血单个核细胞和脾脏白细胞中 Fas-Fas 相关死亡结构域蛋白（CD95 或 APO-1）、FasL-Fas 配体蛋白（CD178）和 TRAIL-TNF 相关凋亡诱导配体（CD253）受体的表达水平，从 38 只患有中度 VL 的有症状狗和 25 只健康狗中进行了评估通过流式细胞术。与健康狗相比，感染狗的血液和脾脏 CD4+和 CD8+细胞的凋亡率更高。与健康狗相比，感染狗血液和脾脏 CD4+细胞中 Fas 和 FasL 的表达水平较低。感染狗的 CD8+细胞中 Fas 的表达较高，而 FasL 的表达较低。仅在感染狗的脾脏 CD8+细胞中观察到 TRAIL 受体的表达增加。FAS 和 Fas-L 阻断抗体证实了这些受体在凋亡中的重要性。我们的研究结果增强了对感染 L. chagasi 的狗的免疫反应的理解，为未来开发减少淋巴细胞耗竭的治疗干预措施提供了帮助。
