Expression of interleukin 4, interleukin 4 splice variants and interferon gamma mRNA in calves experimentally infected with Fasciola hepatica
Expression of interleukin 4, interleukin 4 splice variants and interferon gamma mRNA in calves experimentally infected with Fasciola hepatica
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DOI：
10.1016/j.vetimm.2003.08.002
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发表时间：
2004-01-01
影响因子：
1.8
通讯作者：
Heussler, VT
中科院分区：
文献类型：
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作者：
Waldvogel, AS;Lepage, MF;Heussler, VT
白细胞介素4（IL-4）在辅助性T细胞（Th）2的发育中起主导作用。Th 2免疫应答表达相对大量的白细胞介素4（IL-4）但很少干扰素γ（IFN-γ）是慢性蠕虫感染的特征。但是没有关于牛肝片吸虫（E hepatica）感染早期IL 4表达的信息。因此，我们研究了肝吸虫特异性IL-4和IFN-γ mRNA在实验感染肝吸虫的小牛外周血单个核细胞（PBMC）中的表达。在感染前和接种后第10、28和70天（PID）收集细胞。有趣的是，PBMC对已经在PID 10上的肝内阿米巴分泌-排泄产物（FhSEP）的刺激有反应，并且表达大量的IL-4但不表达IFN-γ mRNA，这表明肝内阿米巴诱导了Th 2偏向的早期免疫应答，其不限于感染部位。感染后IL-4 mRNA表达下降，而IFN-γ mRNA表达略有增加。用FhSEP刺激的分离的淋巴结细胞（LNC），甚至更重要的是，未刺激的LN组织样品表明引流（肝）淋巴结中高度极化的Th 2型免疫应答，但在咽后淋巴结中没有。在初步实验中，检测到牛IL-4 mRNA的两种剪接变体，boIL-4 delta 2和boIL-4 delta 3。由于人IL-4 δ 2被认为是IL-4的竞争性抑制剂，因此了解牛IL-4的这些剪接变体的表达在对肝片吸虫感染的免疫应答期间是否具有调节功能是重要的。事实上，IL-4剪接变异体可以在许多样品中检测到，但定量分析没有产生任何线索，他们的功能。因此，牛IL-4剪接变体的意义仍有待确定。(C)2004 Elsevier B. V.保留所有权利。
Interleukin 4 (IL-4) is expected to play a dominant role in the development of T helper (Th) 2 cells. Th2 immune responses with expression of relatively large amounts of interleukin 4 (IL-4) but little interferon gamma (IFN-gamma) are characteristic for chronic helminth infections. But no information is available about IL4 expression during early Fasciola hepatica (E hepatica) infections in cattle. Therefore, we investigated F hepatica specific IL-4 and IFN-gamma mRNA expression in peripheral blood mononuclear cells (PBMCs) from calves experimentally infected with E hepatica. Cells were collected prior to infection and on post-inoculation days (PIDs) 10, 28 and 70. Interestingly, PBMCs responded to stimulation with E hepatica secretory-excretory products (FhSEP) already on PID 10 and expressed high amounts of IL-4 but not of IFN-gamma mRNA suggesting that E hepatica induced a Th2 biased early immune response which was not restricted to the site of infection. Later in infection IL-4 mRNA expression decreased whereas IFN-gamma mRNA expression increased slightly. Isolated lymph node cells (LNCs) stimulated with FhSEP and, even more importantly, non-stimulated LN tissue samples indicated highly polarized Th2 type immune responses in the draining (hepatic) lymph node, but not in the retropharyngeal lymph node. During preliminary experiments, two splice variants of bovine IL-4 mRNA, boIL-4delta2 and boIL-4delta3, were detected. Since a human IL-4delta2 was assumed to act as competitive inhibitor of IL-4, it was important to know whether expression of these splice variants of bovine IL-4 have a regulatory function during an immune response to infection with F hepatica. Indeed, IL-4 splice variants could be detected in a number of samples, but quantitative analysis did not yield any clue to their function. Therefore, the significance of bovine IL-4 splice variants remains to be determined. (C) 2004 Elsevier B.V. All rights reserved.