Molecular Studies of Immunoparasitology in Snails

描述（由申请人提供）：这是一份竞争性补充申请，旨在响应“使RPG能够利用NCRR中心和类似中心的计划”。该建议是基于我们最近的数据表明免疫信号通路在蜗牛免疫防御中的作用。这项拟议的研究扩展了我目前三年R 01赠款（NIAID，#AI067686）的范围。了解蜗牛Biomphalaria glabrata内部防御的基本机制可能会导致阻断血吸虫病传播的新方法，血吸虫病是一种影响全球2亿人的蜗牛传播疾病。免疫信号通路在进化上是保守的，并且被认为控制大多数免疫相关基因的表达。转录因子是调控特定途径的关键分子。核因子-κ B（NF-？B）和STAT转录因子已显示在体液和细胞免疫应答中起中心作用。尽管在广泛的动物系统发育范围内积累了大量的数据，但对B中这些免疫信号通路的存在和功能一无所知。光滑的我们发现了两个NF-？Bs（BgRel和BgRelish）和来自B的两个STAT（BgSTAT 1和2）。glabrata和检查他们的表达。基于我们的初步数据，我们假设TLR、Imd和Jak/STAT通路在B中是保守的。从功能上讲，为了验证我们的假设，我们建议调查是否TLR，Imd，和Jak/STAT信号通路激活蜗牛后，暴露于S。mansoni本研究结果为钉螺免疫信号转导研究开辟了新的领域，有助于提高对钉螺免疫的认识，最终实现血吸虫病防治的长远目标。 公共卫生相关性：这项研究将有助于我们更好地了解人类血吸虫曼氏血吸虫的中间宿主光滑双脐螺的内部防御的基本机制。这可能导致阻断血吸虫病传播的新方法，血吸虫病是一种影响全球2亿人的蜗牛传播疾病。

DESCRIPTION (provided by applicant): This is a competing supplemental application in response to the Enabling RPGs to Leverage NCRR Center and Center-like Programs. The proposal is made based on our recent data suggesting a role of immune signaling pathways in snail immune defenses. This proposed study extends the scope of my current three-year R01 grant (NIAID, #AI067686). Understanding the fundamental mechanisms of internal defense in the snail Biomphalaria glabrata may lead to new methods for blocking the transmission of schistosomiasis, a snail-borne disease that affects 200 million people worldwide. Immune signaling pathways are evolutionarily conserved and believed to control most immune-related gene expression. Transcription factors are the key molecules regulating a given pathway. The immune signaling pathways TLR (Toll-like receptor), Imd (Immune deficiency), and Jak (Janus kinas)/STAT (signal transducer and activator of transcription) regulated by nuclear factor-kappa B (NF-?B) and STAT transcription factors have been shown to play the central role in humoral and cellular immune responses. In spite of the enormous amount of data accumulated in a wide phylogenetic range of animals, nothing is known about the existence and function of these immune signaling pathways in B. glabrata. We have identified two NF-?Bs (BgRel and BgRelish) and two STATs (BgSTAT1 and 2) from B. glabrata and examined their expression. Based on our preliminary data, we hypothesize that TLR, Imd, and Jak/STAT pathways are conserved in B. glabrata in terms of functionality. To test our hypothesis, we propose to investigate whether TLR, Imd, and Jak/STAT signaling pathways are activated in snails after exposure to S. mansoni. The outcome of this study may open a new area in the studies of snail immune signal transduction, which should improve our understanding of snail immunity and ultimately benefit the long-term goal of schistosomiasis control. PUBLIC HEALTH RELEVANCE: This proposed study will help us in better understanding the fundamental mechanisms of the internal defenses of the snail Biomphalaria glabrata, the intermediate host of human blood fluke Schistosoma mansoni. This may lead to new methods for blocking the transmission of Schistosomiasis, a snail-borne disease that affects 200 million people worldwide.