Echinococcus multilocularis metacestodes modulate cellular cytokine and chemokine release by peripheral blood mononuclear cells in alveolar echinococcosis patients
Echinococcus multilocularis metacestodes modulate cellular cytokine and chemokine release by peripheral blood mononuclear cells in alveolar echinococcosis patients
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DOI：
10.1111/j.1365-2249.2006.03142.x
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发表时间：
2006-08-01
影响因子：
4.6
通讯作者：
Soboslay, P. T.
中科院分区：
文献类型：
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作者：
Huebner, M. P.;Manfras, B. J.;Soboslay, P. T.
多房棘球蚴感染可引起人类肺泡棘球蚴病（AE），这是一种主要影响肝脏的危及生命的疾病。尽管AE严重，但临床症状往往在感染多年后才出现，这表明多房棘球绦虫已经发展出抑制抗寄生虫免疫反应的机制，从而有利于免疫逃避。在本研究中，我们检测了AE患者和健康对照外周血单核细胞（PBMC）对多房棘球绦虫培养上清、活的多房棘球绦虫囊泡和多房棘球绦虫囊泡液抗原的细胞因子、趋化因子的产生和CD分子的表达。共培养48 h后，多房棘球蚴培养上清和多房棘球蚴囊泡均抑制PBMC对促炎细胞因子白细胞介素-12的释放。这种作用是剂量依赖性的，即使用脂多糖（LPS）激活PBMC，也可以观察到肿瘤坏死因子(TNF)- α和IL-12的抑制。比较AE患者与对照组的促炎细胞因子释放，发现AE患者IL-12和tnf - α的释放减少，同时伴有CD4(+) CD25（+）细胞数量增加，Th2型趋化因子CCL17（胸腺和活化调节趋化因子TARC）的释放减少，提示AE患者对多房棘球蚴有抗炎反应。相反，与对照组相比，AE患者的PBMC中干扰素(IFN)- γ的产生和CD4(+) T细胞上CD28的表达增加。这伴随着th2型趋化因子CCL22（巨噬细胞衍生趋化因子，MDC）的较高释放，支持多房棘球绦虫也产生促炎免疫反应。这些结果表明，多房棘球蚴抗原可调节调节性和炎性Th1和Th2细胞因子和趋化因子。这种混合的轮廓可能需要限制寄生虫的生长，但也可以减少宿主体内的寄生周围组织和器官损伤。
Infection with the cestode Echinococcus multilocularis causes human alveolar echinococcosis (AE), a life-threatening disease affecting primarily the liver. Despite the severity of AE, clinical symptoms often develop only many years after infection, which suggests that E. multilocularis has developed mechanisms which depress anti-parasite immune response, thus favouring immune evasion. In this study we examined the production of cytokines, chemokines and the expression of CD molecules on peripheral blood mononuclear cells (PBMC) from AE patients and healthy controls in response to E. multilocularis metacestode culture supernatant, viable E. multilocularis vesicles and E. multilocularis vesicle fluid antigen in vitro. After 48 h of co-culture, E. multilocularis metacestode culture supernatant and E. multilocularis vesicles depressed the release of the proinflammatory cytokine interleukin (IL)-12 by PBMC. This effect was dose-dependent and a suppression of tumour necrosis factor (TNF)-alpha and IL-12 was observed even when PBMC were activated with lipopolysaccharide (LPS). Comparing proinflammatory cytokine release by AE patients and controls showed that the release of IL-12 and TNF-alpha was reduced in AE patients, which was accompanied by an increased number of CD4(+) CD25(+) cells and a reduced release of the Th2 type chemokine CCL17 (thymus and activation regulated chemokine, TARC), suggesting an anti-inflammatory response to E. multilocularis metacestode in AE patients. Instead the production of interferon (IFN)-gamma and the expression of CD28 on CD4(+) T cells were increased in PBMC from AE patients when compared to controls. This was accompanied by a higher release of the Th2-type chemokine CCL22 (macrophage derived chemokine, MDC) supporting that E. multilocularis also generates proinflammatory immune responses. These results indicate that E. multilocularis antigens modulated both regulatory and inflammatory Th1 and Th2 cytokines and chemokines. Such a mixed profile might be required for limiting parasite growth but also for reducing periparasitic tissue and organ damage in the host.