The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responses.
The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responses.
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DOI：
10.1371/journal.pntd.0001593
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发表时间：
2012
影响因子：
3.8
通讯作者：
Dunne DW
中科院分区：
文献类型：
--
作者：
Fitzsimmons CM;Jones FM;Stearn A;Chalmers IW;Hoffmann KF;Wawrzyniak J;Wilson S;Kabatereine NB;Dunne DW
人类 IgE 对 Sm22.6（曼氏血吸虫中的主要 IgE 靶标）的反应与部分免疫的发展相关。该分子位于体皮内部，属于寄生扁形动物的一个蛋白质家族，即体皮过敏原样蛋白 (TAL)。除了包含动力蛋白轻链结构域外，这些 TAL 还包含与许多 EF-hand 过敏原中发现的类似的 EF-hand 结构域。 S. mansoni 基因组搜索显示该物种内有 13 个成员 (SmTAL1-13)。最近的微阵列数据表明它们具有广泛的生命周期转录谱。我们将 SmTAL1 (Sm22.6)、SmTAL2、3、4、5 和 13 表达为重组蛋白，并测量了来自乌干达血吸虫病流行地区的 200 名感染男性（7-60 岁）的 IgE 和 IgG4。对于SmTAL1和3（分别通过成虫和成虫在血吸虫中转录）和SmTAL5（通过成虫在尾蚴中转录），可检测到的IgE反应在7-9岁儿童中很少见，但随着年龄的增长而增加。在所有年龄段，SmTAL2 的 IgE（组成型表达）很少见，而抗 SmTAL2 IgG4 很常见。 SmTAL4 和 13（主要在尾蚴/皮肤阶段转录）的 IgE 和 IgG4 水平均较低。我们尚未测量活寄生虫中的 SmTAL 蛋白丰度或暴露量，但抗体数据向我们表明，在流行地区，长寿命蠕虫的偶尔死亡会引发和增强成虫 SmTAL 的 IgE，持续暴露于垂死的卵会使卵 SmTAL 脱敏，而寄生虫对皮肤的免疫抑制会导致幼虫 SmTAL 的免疫原性较低。其中，蠕虫抗原的 IgE 逐渐增加，与流行地区的年龄依赖性免疫相似。通过检查寄生性曼氏血吸虫的基因组，我们从该生物体的外层（体皮）识别并定义了 13 种过敏原样蛋白家族的结构。我们将这些分子称为曼氏沙门氏菌外皮过敏原样蛋白 (SmTAL)。在曼氏链球菌感染期间，人类宿主会接触侵入皮肤的幼虫、成虫（生活在血液中）和寄生虫卵。这些生命阶段具有非常不同的大小、组织组成和基因表达。我们生产了 6 种具有不同生命周期转录模式的 SmTAL 蛋白，并测量了来自曼氏链球菌流行区的 200 名感染男性对它们的 IgE 抗体反应。 IgE 与外来蛋白质的结合对于过敏很重要，而且对于防御寄生虫也很重要。我们的结果表明，在这些流行地区，长寿线虫的偶尔死亡会引发和增强对成虫 SmTAL 的 IgE 反应，由于持续暴露于垂死的卵而导致对卵 SmTAL 的脱敏，而幼虫 SmTAL 的低免疫原性可能是由于寄生虫对皮肤的免疫抑制所致。血吸虫感染是许多国家的一个主要健康问题。我们的工作深入了解了是什么激发和控制与人类对这种寄生虫的免疫力相关的抗体反应。
A human IgE response to Sm22.6 (a dominant IgE target in Schistosoma mansoni) is associated with the development of partial immunity. Located inside the tegument, the molecule belongs to a family of proteins from parasitic platyhelminths, the Tegument-Allergen-Like proteins (TALs). In addition to containing dynein-light-chain domains, these TALs also contain EF-hand domains similar to those found in numerous EF-hand allergens. S. mansoni genome searches revealed 13 members (SmTAL1-13) within the species. Recent microarray data demonstrated they have a wide range of life-cycle transcriptional profiles. We expressed SmTAL1 (Sm22.6), SmTAL2, 3, 4, 5 and 13 as recombinant proteins and measured IgE and IgG4 in 200 infected males (7–60 years) from a schistosomiasis endemic region in Uganda. For SmTAL1 and 3 (transcribed in schistosomula through adult-worms and adult-worms, respectively) and SmTAL5 (transcribed in cercariae through adult-worms), detectable IgE responses were rare in 7–9 year olds, but increased with age. At all ages, IgE to SmTAL2 (expressed constitutively), was rare while anti-SmTAL2 IgG4 was common. Levels of IgE and IgG4 to SmTAL4 and 13 (transcribed predominantly in the cercariae/skin stage) were all low. We have not measured SmTAL protein abundance or exposure in live parasites, but the antibody data suggests to us that, in endemic areas, there is priming and boosting of IgE to adult-worm SmTALs by occasional death of long-lived worms, desensitization to egg SmTALs through continuous exposure to dying eggs and low immunogenicity of larval SmTALs due to immunosuppression in the skin by the parasite. Of these, it is the gradual increase in IgE to the worm antigens that parallels age-dependent immunity seen in endemic areas. Examining the genome of the parasitic worm Schistosoma mansoni, we have identified and defined the structure of a family of 13 allergen-like proteins from the outer layer (tegument) of the organism. We term these molecules the S. mansoni Tegument-Allergen-Like proteins (SmTALs). During S. mansoni infection the human host is exposed to skin-invading larvae, adult-worms (living in the blood) and to parasite eggs. These life-stages have very different sizes, tissue composition and gene expression. We have produced 6 SmTAL proteins with different life-cycle transcriptional patterns and measured IgE antibody responses to them in 200 infected males from an S. mansoni endemic area. The binding of IgE to foreign proteins is important in allergy but also in defence against parasitic worms. Our results suggest that, in these endemic areas, there is priming and boosting of IgE responses to adult-worm SmTALs by the occasional death of long-lived worms, desensitization to egg SmTALs due to continuous exposure to dying eggs and low immunogenicity of larval SmTALs perhaps due to immunosuppression in the skin by the parasite. Schistosome infection is a major health problem in many countries. Our work provides insight into what provokes and controls the antibody responses associated with human immunity to this parasite.
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影响因子：
1.5
作者：
de Eguino, ADR;Machín, A;Parra, F
通讯作者：
Parra, F
影响因子：
2.1
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华支睾吸虫 21.1 kDa 皮膜蛋白的克隆和表达及其作为吸虫-线虫泛特异性血清诊断抗原的人抗体反应
影响因子：
2
作者：
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通讯作者：
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影响因子：
2.4
作者：
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影响因子：
2.2
作者：
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