Dias Raul Ramos Furtado, Carvalho Eulógio Carlos Queiroz de, Leite Carla Cristina da Silva, Tedesco Roberto Carlos, Calabrese Katia da Silva, Silva Antonio Carlos, DaMatta Renato Augusto, de Fatima Sarro-Silva Maria
Laboratório de Biologia Celular e Tecidual, Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF), 28013-602, Campos dos Goytacazes, RJ, Brazil; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), 21045-900, Rio de Janeiro, RJ, Brazil.
Laboratório de Sanidade Animal, UENF, 28013-602, Campos dos Goytacazes, RJ, Brazil.
PLoS One. 2014 Dec 1;9(12):e113374. doi: 10.1371/journal.pone.0113374. eCollection 2014.
Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.
弓形虫病是一种全球性疾病，大多数感染通过口腔途径发生，并产生各种病理表现，从脑膜脑炎到视网膜脉络膜炎和炎症性肠病。针对这些病症的动物模型稀缺且存在局限性。我们用50或100个ME-49株囊肿经口感染弓形虫，评估了对免疫口服耐受具有极端易感性（TS）或抗性（TR）表型的两系小鼠的感染结果。因此，本研究的目的是评估经弓形虫经口感染的TS和TR小鼠的行为，并确定其作为炎症性疾病研究模型的价值。TR在感染急性期的死亡率，两种剂量均为50%，而TS在分别感染这些剂量后，死亡率为10%和40%。在慢性期，其余的TS死亡，而TR存活了90天。尽管存在心肌炎、肺炎和脑膜脑炎，但TS显示出较高的寄生虫载量，同时肠道炎症和细胞增殖较低。TR出现绒毛和隐窝的大量坏死，类似于炎症性肠病，肠道固有层有淋巴细胞浸润。此外，感染100个囊肿的TR小鼠在眼睛的光感受器层内出现强烈的细胞浸润，视网膜细胞层的排列和形态发生变化以及视网膜脉络膜炎。在感染期间，TS小鼠血清中检测到高水平的IL-6，TR小鼠则出现大量的IFN-γ和TNF-α。两个小鼠品系都出现了不同的疾病结果，但需要强调的是，TR和TS小鼠都出现了感染的急性期和慢性期，这表明这两个品系为研究弓形虫病提供了一个有吸引力的模型。
