Background: Schistosomiasis remains widespread in many regions despite efforts at its elimination. By examining changes in the transcriptome at the host-pathogen interface in the snail Biomphalaria glabrata and the blood fluke Schistosoma mansoni, we previously demonstrated that an early stress response in juvenile snails, manifested by induction of heat shock protein 70 (Hsp 70) and Hsp 90 and of the reverse transcriptase (RT) domain of the B. glabrata non-LTR- retrotransposon, nimbus, were critical for B. glabrata susceptibility to S. mansoni. Subsequently, juvenile B. glabrata BS90 snails, resistant to S. mansoni at 25oC become susceptible by the F2 generation when maintained at 32oC, indicating an epigenetic response. Methodology/Principal Findings: To better understand this plasticity in susceptibility of the BS90 snail, mRNA sequences were examined from S. mansoni exposed juvenile BS90 snails cultured either at 25oC (permissive temperature) or 32oC (non-permissive). Comparative analysis of transcriptomes from snails cultured at the non-permissive and permissive temperatures revealed that whereas stress related transcripts dominated the transcriptome of susceptible BS90 juvenile snails at 32oC, transcripts encoding proteins with a role in epigenetics, such as PIWI (BgPiwi), chromobox protein homolog 1 (BgCBx1), histone acetyl transferase histone deacetylase (HDAC) and metallotransferase (MT) were highly expressed in those cultured at 25oC. To further determine a role for BgPiwi in B. glabrata susceptibility to S. mansoni, siRNA corresponding to the BgPiwi encoding transcript was utilized to suppress expression of BgPiwi, rendering the resistant BS90 juvenile snail susceptible to infection at 25oC. Given transposon silencing activity of PIWI as a facet of its role as guardian of the integrity of the genome, we examined the expression of the nimbus RT encoding transcript at 120 min after infection of resistant BS90 piwi-siRNA treated snails. We observed that nimbus RT was upregulated, indicating that modulation of the transcription of the nimbus RT was associated with susceptibility to S. mansoni in BgPiwi-siRNA treated BS90 snails. Furthermore, treatment of susceptible snails with the RT inhibitor lamivudine, before exposure to S. mansoni, blocked S. mansoni infection concurrent with downregulation of the nimbus RT transcript and upregulation of the BgPiwi encoding transcript in the lamivudine-treated, schistosome-exposed susceptible snails. Conclusions and Significance: These findings support a role for the interplay of BgPiwi and nimbus in the epigenetic modulation of plasticity of resistance/susceptibility in the snail-schistosome relationship.

中文翻译：

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涉及逆转录转座子雨云的PIWI沉默机制在蜗牛媒介Biomphalaria glabrata中调节曼氏血吸虫感染的抗性

背景：尽管在努力消除血吸虫病，但仍在许多地区广泛存在。通过检查蜗牛Biomphalaria glabrata和血吸虫曼氏血吸虫中宿主-病原体界面转录组的变化，我们先前证明了少年蜗牛的早期应激反应，表现为热激蛋白70（Hsp 70）和Hsp的诱导。光滑芽孢杆菌非LTR逆转录转座子nimbus的90和逆转录酶（RT）结构域对于光滑芽孢杆菌对曼氏沙门氏菌的敏感性至关重要。随后，当保持在32oC时，对曼氏沙门氏菌（S. mansoni）产生抵抗力的幼小B. glabrata BS90蜗牛在25oC时易受F2的影响，表明表观遗传反应。方法/主要发现：为了更好地了解BS90蜗牛的可塑性，从在25oC（允许温度）或32oC（非允许）条件下培养的曼氏酵母暴露的少年BS90蜗牛检查mRNA序列。对在非允许和允许温度下培养的蜗牛的转录组进行的比较分析显示，尽管应力相关的转录组在32oC时易感BS90幼体蜗牛的转录组占主导地位，但编码在表观遗传学中起作用的蛋白（例如PIWI（BgPiwi），色盒蛋白）的转录组在25oC下培养的同系物1（BgCBx1），组蛋白乙酰基转移酶，组蛋白脱乙酰基酶（HDAC）和金属转移酶（MT）高度表达。为了进一步确定BgPiwi在甘蓝假单胞菌对曼氏沙门氏菌的易感性中的作用，利用了对应于BgPiwi编码转录本的siRNA来抑制BgPiwi的表达，使抗性BS90幼蜗牛在25oC下容易感染。鉴于PIWI的转座子沉默活性是其作为基因组完整性守护者的一个方面，我们在感染抗性BS90 piwi-siRNA处理的蜗牛后120分钟检查了nimbus RT编码转录本的表达。我们观察到雨云RT上调，表明雨云RT转录的调节与BgPiwi-siRNA处理的BS90蜗牛对曼氏链球菌的敏感性有关。此外，在暴露于曼氏沙门氏菌之前，用RT抑制剂拉米夫定治疗易感蜗牛可阻止曼氏沙门氏菌感染，同时拉米夫定治疗，血吸虫暴露的易感性蜗牛中雨云RT转录本的下调和BgPiwi编码转录本的上调。 。