Trichinella spiralis-secreted products modulate DC functionality and expand regulatory T cells in vitro
Trichinella spiralis-secreted products modulate DC functionality and expand regulatory T cells in vitro
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DOI：
10.1111/j.1365-3024.2012.01353.x
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发表时间：
2012-04-01
影响因子：
2.2
通讯作者：
Pinelli, E.
中科院分区：
文献类型：
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作者：
Aranzamendi, C.;Fransen, F.;Pinelli, E.
蠕虫及其产物可以抑制宿主的免疫反应，这可能有利于寄生虫的生存。旋毛虫可以在包括人类和小鼠在内的多种哺乳动物宿主中建立慢性感染。本文旨在研究旋毛虫肌幼虫排泄/分泌产物（TspES）对DC功能和T细胞活化的影响。我们发现TspES抑制由来自肠杆菌的S-和R-形式脂多糖（LPS）诱导的体外DC成熟。使用不同的Toll样受体（TLR）激动剂，我们表明TspES对DC成熟的抑制作用仅限于TLR 4。这些蠕虫产物也干扰与TLR介导的信号转导途径相关的几个基因的表达。为了研究TspES对T细胞活化的影响，我们使用来源于OVA-TCR转基因D011.10的脾细胞，其与OVA和TspES脉冲的DC一起孵育。结果表明，TspES的存在导致CD 4 + CD 25 + Foxp 3 + T细胞的扩增。这些调节性T（Treg）细胞被证明具有抑制活性并产生TGF-β。总之，这些结果表明旋毛虫分泌产物可以抑制DC成熟并诱导功能性Treg细胞的体外扩增。
Helminths and their products can suppress the host immune response which may benefit parasite survival. Trichinella spiralis can establish chronic infections in a wide range of mammalian hosts including humans and mice. Here, we aim at studying the effect of T.spiralis muscle larvae excretory/secretory products (TspES) on the functionality of DC and T cell activation. We found that TspES suppress in vitro DC maturation induced by both S- and R-form lipopolysaccharide(LPS) from enterobacteria. Using different toll-like receptor (TLR) agonists, we show that the suppressive effect of TspES on DC maturation is restricted to TLR4. These helminth products also interfere with the expression of several genes related to the TLR-mediated signal transduction pathways. To investigate the effect of TspES on T cell activation, we used splenocytes derived from OVA-TCR transgenic D011.10 that were incubated with OVA and TspES-pulsed DC. Results indicate that the presence of TspES resulted in the expansion of CD4+ CD25+ Foxp3+ T cells. These regulatory T (Treg) cells were shown to have suppressive activity and to produce TGF-beta. Together these results suggest that T.spiralis secretion products can suppress DC maturation and induce the expansion of functional Treg cells in vitro.