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重组班氏丝虫表面蛋白(WSP)诱导的感染期班氏丝虫的 T 细胞反应。

Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections.

机构信息

Centre for Biotechnology, Anna University, Chennai 600025, India.

出版信息

Parasitol Res. 2012 Feb;110(2):787-97. doi: 10.1007/s00436-011-2553-7. Epub 2011 Jul 23.

Abstract

Human lymphatic filariasis is a debilitating parasitic disease characterized by downregulation of the host's immune response in asymptomatic carriers along with profound hyperreactivity in chronic patients apart from putatively immune endemic normals. The endosymbiont Wolbachia, a bacterium of filarial nematodes has received much attention as possible chemotherapeutic target and its involvement in disease pathogenesis. The role of recombinant Wolbachia surface protein (rWSP), one of the most abundantly expressed proteins of the endosymbiont, in modulating cell-mediated immune responses in patients harboring Wuchereria bancrofti infections was evaluated in the current study. rWSP-induced lymphoproliferation with peripheral blood mononuclear cells suggested an impaired proliferative response in asymptomatic microfilaremic (MF) and symptomatic chronic pathology (CP) patients compared to endemic normals (EN). This was further supported by a significantly diminished expression of CD69 along with elevated levels of CD127 and CD62L in filarial patients (MF and CP) compared to EN. Further, rWSP induced the expression of regulatory T cell markers CTLA-4 and CD25 along with suppressor cytokines IL-10 and TGF-β in MF and CP patients compared to EN. However, the rWSP-stimulated expression of IFN-γ was diminished significantly in filarial patients compared to endemic normals. Thus, these findings suggest that WSP may also contribute to the suppression of immune responses seen in filarial patients.

摘要

人淋巴丝虫病是一种使人虚弱的寄生虫病,其特征是无症状感染者体内的宿主免疫反应下调,而慢性患者则表现出明显的高反应性,此外还有潜在的免疫地方性正常者。内共生菌沃尔巴克氏体(一种丝虫线虫的细菌)作为可能的化学治疗靶点,及其在疾病发病机制中的作用,受到了广泛关注。本研究评估了重组沃尔巴克氏体表面蛋白(rWSP)在调节携带班氏丝虫感染的患者细胞介导免疫反应中的作用。rWSP 诱导外周血单个核细胞增殖,表明无症状微丝蚴血症(MF)和有症状慢性病理(CP)患者的增殖反应受损,与地方性正常者(EN)相比。这一结果得到了进一步的支持,即与 EN 相比,丝虫病患者(MF 和 CP)中 CD69 的表达明显降低,同时 CD127 和 CD62L 的水平升高。此外,与 EN 相比,rWSP 在 MF 和 CP 患者中诱导调节性 T 细胞标记物 CTLA-4 和 CD25 的表达以及抑制性细胞因子 IL-10 和 TGF-β 的表达。然而,与地方性正常者相比,丝虫病患者 rWSP 刺激产生的 IFN-γ 显著减少。因此,这些发现表明 WSP 也可能有助于抑制丝虫病患者的免疫反应。

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