TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni.
TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni.
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TGF-β信号传导控制寄生虫烟瘤曼森的胚胎发育。
DOI：
10.1371/journal.ppat.0030052
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发表时间：
2007-04
期刊：
影响因子：
6.7
通讯作者：
Pearce EJ
中科院分区：
文献类型：
--
作者：
Freitas TC;Jung E;Pearce EJ
超过2亿人患有收缩的风险超过6亿，这是主要被忽视的热带疾病之一。但是，人类的宿主。由于卵产生在传播和疾病中的核心，对分泌的鸡蛋抗原的免疫反应引起的变化很少，这对这种新的生命阶段的发展是相对较少的。寄生虫编码的TGF-β超家族成员Mansoni抑制素/活化素（SMINACT），这是该过程的关键将SMINACT表达在成年女性的生殖组织中，实时RT-PCR分析表明，Sminact在Oviposing fater的女性及其产生的卵中明确表达，但基于实时的RT-PCR分析。在降低的水平下，在不存在繁殖的单性感染和IL-7R - / - 小鼠的寄生虫中分离出的成年蠕虫中，其中可行的卵生产严重损害，西方的分析表明，来自单性感染的寄生虫和IL-7R - / - 小鼠的感染是无法检测到的Sminact在成功的胚胎发生中的关键作用是通过发现RNA干扰介导的卵中的Sminact表达敲低的发现开发。我们的结果表明，TGF-β信号传导在多宗寄生虫的胚胎发生中起主要作用，并且对发展和预防重要和被忽视的人类疾病的新策略具有影响。
血块是寄生虫蠕虫，由于他们生产的卵旨在从宿主中释放以允许感染而引起数亿人的疾病。诸如肝脏的靶向器官会影响女性血块的卵产生。 （违反直觉）关于宿主免疫系统的信号的贡献。鸡蛋。只有在具有免疫学胜任的男性配对时，就可以使用该基因编码的蛋白质。在血块中抑制，我们表明该基因的产物在卵发育中起着至关重要的作用。此外，该基因在卵中的关键作用使其成为阻止传播和疾病发展的潜在目标。
Over 200 million people have, and another 600 million are at risk of contracting, schistosomiasis, one of the major neglected tropical diseases. Transmission of this infection, which is caused by helminth parasites of the genus Schistosoma, depends upon the release of parasite eggs from the human host. However, approximately 50% of eggs produced by schistosomes fail to reach the external environment, but instead become trapped in host tissues where pathological changes caused by the immune responses to secreted egg antigens precipitate disease. Despite the central importance of egg production in transmission and disease, relatively little is understood of the molecular processes underlying the development of this key life stage in schistosomes. Here, we describe a novel parasite-encoded TGF-β superfamily member, Schistosoma mansoni Inhibin/Activin (SmInAct), which is key to this process. In situ hybridization localizes SmInAct expression to the reproductive tissues of the adult female, and real-time RT-PCR analyses indicate that SmInAct is abundantly expressed in ovipositing females and the eggs they produce. Based on real-time RT-PCR analyses, SmInAct transcription continues, albeit at a reduced level, both in adult worms isolated from single-sex infections, where reproduction is absent, and in parasites from IL-7R−/− mice, in which viable egg production is severely compromised. Nevertheless, Western analyses demonstrate that SmInAct protein is undetectable in parasites from single-sex infections and from infections of IL-7R−/− mice, suggesting that SmInAct expression is tightly linked to the reproductive potential of the worms. A crucial role for SmInAct in successful embryogenesis is indicated by the finding that RNA interference–mediated knockdown of SmInAct expression in eggs aborts their development. Our results demonstrate that TGF-β signaling plays a major role in the embryogenesis of a metazoan parasite, and have implications for the development of new strategies for the treatment and prevention of an important and neglected human disease. Schistosomes are parasitic worms that infect hundreds of millions of people in developing countries. They cause disease by virtue of the fact that the eggs that they produce, which are intended for release from the host in order to allow transmission of infection, can become trapped in target organs such as the liver, where they induce damaging inflammation. Egg production by female schistosomes is critically dependent on the presence of male parasites, without which females never fully develop, and (counterintuitively) on the contribution of signals from the host's immune system. Very little is understood about the molecular basis of these interactions. Here, we describe a newly discovered schistosome gene, which is expressed in the reproductive tract of the female parasite and in parasite eggs. The protein encoded by this gene is made only when females are paired with males in an immunologically competent setting. Using recently developed tools that allow gene function to be inhibited in schistosomes, we show that the product of this gene plays a crucial role in egg development. Examining how the expression of this gene is controlled has the potential to provide insight into the molecular nature of the interactions between male and female parasites and their hosts. Moreover, the pivotal role of this gene in the egg makes it a potential target for blocking transmission and disease development.
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影响因子：
1.5
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通讯作者：
Yoshino, TP
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