The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production
The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production
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DOI：
10.1016/j.ijpara.2011.08.005
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发表时间：
2011-11-01
影响因子：
4
通讯作者：
Mountford, Adrian P.
中科院分区：
文献类型：
--
作者：
Paveley, Ross A.;Aynsley, Sarah A.;Mountford, Adrian P.
在这项研究中，寄生蠕虫曼氏血吸虫的感染性幼虫被证明含有大量的甘露糖受体（MR; CD 206），这是一个重要的模式识别受体（PRR）的先天免疫系统的特异性糖基化成分。MR配体特别丰富的排泄/分泌（E/S）的物质释放转化的尾蚴成童虫，感染宿主的一个关键过程。E/S材料的羧基荧光素二乙酸琥珀酰亚胺酯（CFDA-SE）标记的尾蚴表现出增强的结合细胞系，过度表达MR。相反，吸收显着降低骨髓来源的巨噬细胞（M Phi）从MR-/-小鼠，虽然他们更活跃的判断增强促炎细胞因子的产生和CD 40的表达。MR-/-小鼠自然经皮感染CFDA-SE标记的寄生虫后，与野生型小鼠相比，皮肤和引流淋巴结中CFDA-SE+的细胞较少，这意味着幼虫寄生虫抗原的摄取和呈递减少。然而，皮肤引流淋巴结细胞的抗原特异性增殖显著增强，它们分泌的IFN γ水平显著升高，但IL-4水平降低。总之，我们表明，皮肤中丰富的单核吞噬细胞上的MR在内化寄生虫侵入阶段释放的E/S物质方面发挥着重要作用，从而调节其促炎细胞因子的产生。在缺乏MR的情况下，抗原特异性CD 4（+）细胞是Th 1偏向的，这表明由棘球蚴幼虫释放的糖基化E/S物质连接MR调节了CD 4（+）细胞特异性IFN γ的产生。(C)2011年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
In this study, infective larvae of the parasitic helminth Schistosoma mansoni were shown to contain a large number of glycosylated components specific for the Mannose Receptor (MR; CD206), which is an important pattern recognition receptor (PRR) of the innate immune system. MR ligands were particularly rich in excretory/secretory (E/S) material released during transformation of cercariae into schistosomula, a process critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled cercariae showed enhanced binding by cells lines that over-express the MR. Conversely, uptake was significantly lower by bone marrow-derived macrophages (M Phi) from MR-/- mice, although they were more active as judged by enhanced pro-inflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR-/- mice with CFDA-SE-labelled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE+ compared with wild-type mice, implying reduced uptake and presentation of larval parasite antigen. However, antigen-specific proliferation of skin draining lymph node cells was significantly enhanced and they secreted markedly elevated levels of IFN gamma but decreased levels of IL-4. In conclusion, we show that the MR on mononuclear phagocytic cells, which are plentiful in the skin, plays a significant role in internalising E/S material released by the invasive stages of the parasite which in turn modulates their production of pro-inflammatory cytokines. In the absence of the MR, antigen-specific CD4(+) cells are Th1 biased, suggesting that ligation of the MR by glycosylated E/S material released by schistosome larvae modulates the production of CD4(+) cell specific IFN gamma. (C) 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.