deSchoolmeester Matthew L, Martinez-Pomares Luisa, Gordon Siamon, Else Kathryn J
Faculty of Life Sciences, University of Manchester, Manchester, UK.
Immunology. 2009 Feb;126(2):246-55. doi: 10.1111/j.1365-2567.2008.02893.x. Epub 2008 Jun 27.
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.
毛首鞭形线虫是人类胃肠道线虫寄生虫毛首鞭形线虫的天然小鼠模型,并且已经明确,蠕虫排出需要以2型辅助性T细胞为主导的免疫反应。感染期间巨噬细胞在小鼠大肠中积聚,已知这些细胞表达甘露糖受体(MR),其可能作为模式识别受体。此处呈现的数据首次表明,毛首鞭形线虫排泄/分泌产物(E/S)诱导骨髓来源的巨噬细胞(BMDM)产生多种细胞因子并具有MR结合活性。使用来自MR基因敲除小鼠的替代性活化BMDM表明,白细胞介素-6的产生部分依赖于MR。用毛首鞭形线虫感染MR基因敲除小鼠表明,该受体对于寄生虫的排出并非必需,因为MR基因敲除小鼠排出寄生虫的动力学与野生型动物相同,并且在肠系膜淋巴结中具有相似的细胞因子反应。此外,尽管MR的缺失可降低促炎介质的血清水平,但通过巨噬细胞流入、杯状细胞增生和隐窝深度评估时,MR的缺失在毛首鞭形线虫感染后不会导致肠道炎症增加。这项研究表明,尽管MR可结合毛首鞭形线虫E/S的成分,但它并非对该寄生虫免疫反应的产生至关重要。