Omega-1 & IPSE paralogues analysis.

The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg “winners” attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg “losers” carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped “losers” instead of migrating intestinal “winners”. This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite’s eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.

曼氏血吸虫（Schistosoma mansoni）的虫卵是慢性血吸虫病临床表现的主要诱因。虫卵产出后，“成功”虫卵会黏附于肠系膜静脉内皮，经一段发育周期后诱导形成小型肉芽肿，借此协助自身迁移至肠腔；而随血流被带至非特异性组织的“失败”虫卵同样可完成完整发育，并诱导大型肉芽肿形成，但其生命周期会在此终止。尽管这些被困的虫卵属于寄生虫生命周期中的死胡同，但绝大多数旨在解析曼氏血吸虫虫卵生物学特性的研究，均以滞留在肝脏内的“失败”虫卵为研究对象，而非成功迁移至肠道的“成功”虫卵。这引出了一个核心科学问题：这两类虫卵存在何种差异？通过对感染7周后分离得到的曼氏血吸虫虫卵开展严谨的比较转录组学分析，本研究证实：无论处于发育早期还是晚期阶段，基因表达均显著依赖于虫卵的组织定位。成熟肠道虫卵中，线粒体基因与毒液过敏原样蛋白的表达水平显著上调；而此前已被充分表征的虫卵免疫调节因子IPSE/alpha-1与omega-1，以及微外显子基因，则主要在肝脏虫卵中表达。此外，若干此前被证实参与虫卵-宿主互作的蛋白酶与蛋白酶抑制剂，也呈现出明确的组织特异性基因表达模式。这些显著的基因表达差异，可体现在肝脏与肠道可溶性虫卵抗原诱发宿主免疫应答的能力差异上，也能解释肝脏虫卵孵出的毛蚴（miracidia）寿命更短的现象。本次比较分析为寄生虫虫卵在发育进程与组织定位背景下的生物学特性提供了全新视角。本研究结果有助于更全面、准确地理解寄生虫虫卵与宿主的互作机制——过往相关研究往往仅以肝脏虫卵为研究对象，有时还会得出不够精准的泛化结论。