Differential Gamma Interferon-and Tumor Necrosis Factor Alpha-Driven Cytokine Response Distinguishes Acute Infection of a Metatherian Host with Toxoplasma gondii and Neospora caninum
Differential Gamma Interferon-and Tumor Necrosis Factor Alpha-Driven Cytokine Response Distinguishes Acute Infection of a Metatherian Host with Toxoplasma gondii and Neospora caninum
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DOI：
10.1128/iai.00173-17
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发表时间：
2017-06-01
影响因子：
3.1
通讯作者：
Slapeta, Jan
中科院分区：
文献类型：
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作者：
Donahoe, Shannon L.;Phalen, David N.;Slapeta, Jan
弓形虫和犬新孢子虫(都是尖端复合体)是密切相关的形成包囊的球虫寄生虫，它们的寄主范围和致病能力有很大差异。与真兽类哺乳动物不同，澳大利亚有袋类动物(变态哺乳动物)长期以来一直被认为非常容易感染弓形虫病和新孢子病，因为它们在历史上与寄生虫隔绝。本研究以肉食性肥尾沙鼠(Sminthopsis Crassicaudata)为疾病模型，研究了澳大利亚袋类动物对弓形虫和犬沙鼠的免疫应答和易感性。从疾病的严重临床和组织病理学特征以及被评估的组织中较高的组织寄生虫负担来看，感染犬弓形虫的邓纳特人的疾病结局比感染弓形虫的邓纳特人更严重。用转录组测序(RNA-SEQ)检测感染脾细胞和有丝分裂原刺激的脾细胞的细胞因子谱。用定量逆转录聚合酶链式反应(qRT-PCR)检测关键Th1(干扰素和肿瘤坏死因子α)、Th2(IL-4和IL-6)和Th17(IL-17A)细胞因子在感染过程中的表达变化。结果表明，大尾巴对犬弓形体和弓形虫感染的细胞因子反应存在质的差异。感染弓形虫的Dunnarts能够比感染犬弓形虫的人产生更有效的Th1免疫反应，这表明免疫反应在这种有袋哺乳动物寄生虫感染的后果中所起的作用。
Toxoplasma gondii and Neospora caninum (both Apicomplexa) are closely related cyst-forming coccidian parasites that differ significantly in their host ranges and ability to cause disease. Unlike eutherian mammals, Australian marsupials (metatherian mammals) have long been thought to be highly susceptible to toxoplasmosis and neosporosis because of their historical isolation from the parasites. In this study, the carnivorous fat-tailed dunnart (Sminthopsis crassicaudata) was used as a disease model to investigate the immune response and susceptibility to infection of an Australian marsupial to T. gondii and N. caninum. The disease outcome was more severe in N. caninuminfected dunnarts than in T. gondii-infected dunnarts, as shown by the severity of clinical and histopathological features of disease and higher tissue parasite burdens in the tissues evaluated. Transcriptome sequencing (RNA-seq) of spleens from infected dunnarts and mitogen-stimulated dunnart splenocytes was used to define the cytokine repertoires. Changes in mRNA expression during the time course of infection were measured using quantitative reverse transcription-PCR (qRT-PCR) for key Th1 (gamma interferon [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]), Th2 (interleukin 4 [IL-4] and IL-6), and Th17 (IL-17A) cytokines. The results show qualitative differences in cytokine responses by the fat-tailed dunnart to infection with N. caninum and T. gondii. Dunnarts infected with T. gondii were capable of mounting a more effective Th1 immune response than those infected with N. caninum, indicating the role of the immune response in the outcome scenarios of parasite infection in this marsupial mammal.