Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta
Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta
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DOI：
10.1017/s0031182004006985
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发表时间：
2005-05-01
期刊：
影响因子：
2.4
通讯作者：
McKay, DM
中科院分区：
文献类型：
--
作者：
Wang, A;McKay, DM
寄主-寄生虫的关系非常具体。在利用宿主生态位的过程中，多种寄生虫已被证明可以直接操纵宿主的免疫反应。我们评估了小膜膜绦虫全虫提取物调节免疫细胞激活的能力。分别用T细胞有丝分裂原、豆豆蛋白A (cona) h . diminuta提取物激活人血液或啮齿动物脾脏的免疫细胞，并在处理后24和72 h采用ELISA和[h -3]胸腺嘧啶并入检测细胞因子（IL-2、-4、- 10、-12）的产生和增殖。与H. diminuta提取物（100 μ g蛋白/ml）共处理几乎消除了Con - a诱导的免疫细胞增殖，这不是由于细胞凋亡增加。蠕虫提取物的煮沸降低了其抗增殖作用，分离表明> 50 kDa成分主要负责抑制Con - a诱导的免疫细胞增殖。细胞因子测定结果显示，小红花提取物显著降低Con a刺激的IL-2和IL-4，但增加IFN γ、IL-12和IL-10的产生。增加的IL-12是由于提取物中的LPS污染和蠕虫衍生的‘IL-12’样肽在ELISA和Western blots中结合。相比之下，H. diminua衍生因子直接刺激常规脾细胞产生IL-10，并且污染LPS协同增强IL-10的产生。因此，H. diminuta有可能阻断受刺激的T细胞增殖，并通过抑制IL-4和促进IL-10的产生，可能使免疫环境偏向免疫调节之一，远离IL-4主导的T辅助2型事件。
The host-parasite relationship is exquisitely specific. In exploiting the host niche, a variety of helminth parasites have been shown to directly manipulate their hosts' immune responses. We assessed the ability of a whole-worm extract of Hymenolepis diminuta to modulate immune cell activation. Immune cells isolated from human blood or rodent spleens were activated with the T cell mitogen, concanavalin A (Con A) H. diminuta extract and cytokine production (i.e. IL-2, -4, - 10, -12) and proliferation assessed by ELISA and [H-3]thymidine incorporation 24 and 72 h post-treatment, respectively. Co-treatment with the H. diminuta extract (100 mu g protein/ml) virtually abolished Con A-induced immune cell proliferation, which was not due to increased apoptosis. Boiling of the worm extract reduced its anti-proliferative effect and fractionation indicated that a > 50 kDa component was predominantly responsible for the inhibition of Con A-induced immune cell proliferation. Cytokine determinations revealed that the H. diminuta extract significantly reduced Con A-stimulated IL-2 and IL-4, but enhanced the production of IFN gamma, IL-12 and IL-10. The increased IL-12 was due to an LPS contaminant in the extract and a helminth - derived 'IL-12'-like peptide that bound in the ELISA and Western blots. In contrast, a H. diminuta-derived factor directly stimulated IL-10 production by routine splenocytes, and contaminating LPS synergistically enhanced the production of IL-10. Thus, H. diminuta has the potential to block stimulated T cell proliferation and, by inhibiting IL-4 and promoting IL-10 production, may bias the immune environment towards one of immunoregulation and away from IL-4 dominated T helper 2 type events.