Beineke A, Puff C, Seehusen F, Baumgärtner W
Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
Vet Immunol Immunopathol. 2009 Jan 15;127(1-2):1-18. doi: 10.1016/j.vetimm.2008.09.023. Epub 2008 Oct 4.
Canine distemper is a worldwide occurring infectious disease of dogs, caused by a morbillivirus, closely related to measles and rinderpest virus. The natural host range comprises predominantly carnivores. Canine distemper virus (CDV), an enveloped, negative-sense RNA virus, infects different cell types, including epithelial, mesenchymal, neuroendocrine and hematopoietic cells of various organs and tissues. CDV infection of dogs is characterized by a systemic and/or nervous clinical course and viral persistence in selected organs including the central nervous system (CNS) and lymphoid tissue. Main manifestations include respiratory and gastrointestinal signs, immunosuppression and demyelinating leukoencephalomyelitis (DL). Impaired immune function, associated with depletion of lymphoid organs, consists of a viremia-associated loss of lymphocytes, especially of CD4+ T cells, due to lymphoid cell apoptosis in the early phase. After clearance of the virus from the peripheral blood an assumed diminished antigen presentation and altered lymphocyte maturation cause an ongoing immunosuppression despite repopulation of lymphoid organs. The early phase of DL is a sequel of a direct virus-mediated damage and infiltrating CD8+ cytotoxic T cells associated with an up-regulation of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha and IL-12 and a lacking response of immunomodulatory cytokines such as IL-10 and transforming growth factor (TGF)-beta. A CD4+-mediated delayed type hypersensitivity and cytotoxic CD8+ T cells contribute to myelin loss in the chronic phase. Additionally, up-regulation of interferon-gamma and IL-1 may occur in advanced lesions. Moreover, an altered balance between matrix metalloproteinases and their inhibitors seems to play a pivotal role for the pathogenesis of DL. Summarized, DL represents a biphasic disease process consisting of an initial direct virus-mediated process and immune-mediated plaque progression. Immunosuppression is due to early virus-mediated lymphocytolysis followed by still poorly understood mechanisms affecting antigen presentation and lymphocyte maturation.
犬瘟热是一种在全球范围内发生的犬类传染病，由一种麻疹病毒引起，与麻疹病毒和牛瘟病毒密切相关。其自然宿主范围主要包括食肉动物。犬瘟热病毒（CDV）是一种有包膜的负链RNA病毒，可感染不同类型的细胞，包括各种器官和组织的上皮细胞、间充质细胞、神经内分泌细胞和造血细胞。犬感染CDV的特征是全身性和/或神经性临床病程以及病毒在包括中枢神经系统（CNS）和淋巴组织在内的特定器官中持续存在。主要表现包括呼吸道和胃肠道症状、免疫抑制和脱髓鞘性白质脑脊髓炎（DL）。免疫功能受损与淋巴器官耗竭有关，在疾病早期，由于淋巴样细胞凋亡，导致与病毒血症相关的淋巴细胞损失，尤其是CD4+T细胞。病毒从外周血清除后，尽管淋巴器官重新填充，但推测抗原呈递减少和淋巴细胞成熟改变会导致持续的免疫抑制。DL的早期阶段是直接病毒介导损伤和浸润性CD8+细胞毒性T细胞的结果，与促炎细胞因子如白细胞介素（IL）-6、IL-8、肿瘤坏死因子（TNF）-α和IL-12的上调以及免疫调节细胞因子如IL-10和转化生长因子（TGF）-β的反应缺乏有关。在慢性期，CD4+介导的迟发型超敏反应和细胞毒性CD8+T细胞导致髓鞘丢失。此外，在晚期病变中可能会出现干扰素-γ和IL-1的上调。此外，基质金属蛋白酶及其抑制剂之间平衡的改变似乎在DL的发病机制中起关键作用。总之，DL代表了一个双相疾病过程，包括最初的直接病毒介导过程和免疫介导的斑块进展。免疫抑制是由于早期病毒介导的淋巴细胞溶解，随后是影响抗原呈递和淋巴细胞成熟的机制仍不清楚。
