Cloning of Syrian hamster (Mesocricetus auratus) cytokine cDNAs and analysis of cytokine mRNA expression in experimental visceral leishmaniasis
Cloning of Syrian hamster (Mesocricetus auratus) cytokine cDNAs and analysis of cytokine mRNA expression in experimental visceral leishmaniasis
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DOI：
10.1128/iai.66.5.2135-2142.1998
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发表时间：
1998-05-01
影响因子：
3.1
通讯作者：
Freeman, GL
中科院分区：
文献类型：
--
作者：
Melby, PC;Tryon, VV;Freeman, GL
叙利亚金黄仓鼠（Mesocricetus auratus）独特地对多种细胞内病原体敏感，并且是许多人类感染性疾病的极好模型，这种高水平敏感性的分子基础是未知的，并且与这种模型相关的免疫学研究受到缺乏可用试剂的限制，在这份报告中，我们描述了克隆和序列分析的部分叙利亚仓鼠白细胞介素2（IL-2），IL-4，γ干扰素，此外，我们在该动物模型中检测了细胞因子对细胞内原生动物杜氏利什曼原虫感染的应答，仓鼠细胞因子的序列分析显示与相应的小鼠、大鼠和人核苷酸序列的同源性为69 - 93%，与推导的氨基酸序列的同源性为48 - 100%。与小鼠和大鼠同源物相比，仓鼠IFN-γ，在C末端有额外的17个氨基酸，可以降低该分子的生物活性，从而导致该动物对细胞内病原体的极端易感性。这些基因在感染L.用北方印迹法测定了内脏利什曼病（VL）的致病菌donovani。仓鼠中的VL是一种进行性、致命的疾病，非常接近于活动性人类疾病，在该模型中，Th 1细胞因子mRNA明显表达，早在感染后1周就检测到转录本，未感染仓鼠中IL-4的基础表达是突出的，但没有增加对L.感染的反应。donovani的研究中，在感染的动物中检测到低水平的IL-12转录物表达，并且证实了IFN-γ的表达。IL-10（一种有效的巨噬细胞灭活剂）的表达在整个感染过程中增加，并且可能有助于这种感染的进行性。这些初步的研究是第一次检查的分子免疫发病机制的仓鼠模型VL感染，并表明，进行性疾病在这个模型中的VL是不相关的脾细胞免疫应答的早期极化向Th 2表型和远离Th 1表型。
The Syrian golden hamster (Mesocricetus auratus) is uniquely susceptible to a variety of intracellular pathogens and is an excellent model for a number of human infectious diseases, The molecular basis for this high level of susceptibility is unknown, and immunological studies related to this model have been limited by the lack of available reagents, In this report we describe the cloning and sequence analysis of portions of the Syrian hamster interleukin 2 (IL-2), IL-4, gamma interferon (IFN-gamma), tumor necrosis factor alpha, IL-10, IL-12p40, and transforming growth factor beta cDNAs, In addition, we examined the cytokine response to infection with the intracellular protozoan Leishmania donovani in this animal model, Sequence analysis of the hamster cytokines revealed 69 to 93% homology with the corresponding mouse, rat, and human nucleotide sequences and 48 to 100% homology with the deduced amino acid sequences, The hamster IFN-gamma, compared with the mouse and rat homologs, had an additional 17 amino acids at the C terminus that could decrease the biological activity of this molecule and thus contribute to the extreme susceptibility of this animal to intracellular pathogens. The splenic expression of these genes in response to infection with L. donovani, the cause of visceral leishmaniasis (VL), was determined by Northern blotting. VL in the hamster is a progressive, lethal disease which very closely mimics active human disease, In this model there was pronounced expression of the Th1 cytokine mRNAs, with transcripts being detected as early as 1 week postinfection, Basal expression of IL-4 in uninfected hamsters was prominent but did not increase in response to infection with L. donovani, IL-12 transcript expression was detected at low levels in infected animals and paralleled the expression of IFN-gamma, Expression of IL-10, a potent macrophage deactivator, increased throughout the course of infection and could contribute to the progressive nature of this infection. These initial studies are the first to examine the molecular immunopathogenesis of a hamster model of VL infection and indicate that progressive disease in this model of VL is not associated with early polarization of the splenic cellular immune response toward a Th2 phenotype and away from a Th1 phenotype.