The mannose receptor binds Trichuris muris excretory/secretory proteins but is not essential for protective immunity
The mannose receptor binds Trichuris muris excretory/secretory proteins but is not essential for protective immunity
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DOI：
10.1111/j.1365-2567.2008.02893.x
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发表时间：
2009-02-01
期刊：
影响因子：
6.4
通讯作者：
Else, Kathryn J.
中科院分区：
文献类型：
--
作者：
deSchoolmeester, Matthew L.;Martinez-Pomares, Luisa;Else, Kathryn J.
鼠鞭虫是人胃肠道线虫寄生虫鞭虫的天然小鼠模型，并且已经充分确定，驱虫需要T辅助细胞2型主导的免疫应答。巨噬细胞在感染期间在小鼠的大肠中积累，并且已知这些细胞表达甘露糖受体（MR），其可以充当模式识别受体。本文的数据首次表明T.小鼠排泄分泌产物（E/S）诱导骨髓源性巨噬细胞（BMDM）产生多种细胞因子并具有MR结合活性。利用MR基因敲除小鼠的交替活化的BMDM，表明白细胞介素-6的产生部分依赖于MR。muris的研究揭示了这种受体对于寄生虫的排出不是必需的，因为MR敲除小鼠以与野生型动物相同的动力学排出寄生虫，并且在肠系膜淋巴结中具有相似的细胞因子应答。此外，尽管作用于降低促炎介质的血清水平，MR的缺乏不会导致T.当通过巨噬细胞流入、杯状细胞增生和隐窝深度评估时，这项工作表明，尽管T。muris E/S，MR并不关键地参与对该寄生虫的免疫应答的产生。
Trichuris muris is a natural mouse model of the human gastrointestinal nematode parasite Trichuris trichiura and it is well established that a T helper type 2-dominated immune response is required for worm expulsion. Macrophages accumulate in the large intestine of mice during infection and these cells are known to express the mannose receptor (MR), which may act as a pattern recognition receptor. The data presented here show for the first time that T. muris excretory/secretory products (E/S) induce bone-marrow-derived macrophages (BMDM) to produce several cytokines and have MR-binding activity. Using alternatively activated BMDM from MR knockout mice it is shown that the production of interleukin-6 partially depends on the MR. Infection of MR knockout mice with T. muris reveals that this receptor is not necessary for the expulsion of the parasite because MR knockout mice expel parasites with the same kinetics as wild-type animals and have similar cytokine responses in the mesenteric lymph nodes. Furthermore, despite acting to reduce serum levels of proinflammatory mediators, absence of the MR does not lead to increased gut inflammation after T. muris infection when assessed by macrophage influx, goblet cell hyperplasia and crypt depth. This work suggests that, despite binding components of T. muris E/S, the MR is not critically involved in the generation of the immune response to this parasite.