Unveiling the conserved mechanism of microsporidian vertical transmission: A comparative study of <i>Nosema</i> infection across host species

Microsporidia, ubiquitous obligate intracellular parasites infecting a wide range of hosts from humans to economically vital animals, employ transovarial transmission (TOT) as their primary vertical transmission mode. Despite its significance, the mechanisms underpinning microsporidian TOT have remained elusive. This study comparatively analyzed the TOT in two distinct systems: <i>Nosema pernyi</i> infecting wild tussah <i>Antheraea pernyi</i>, and <i>Nosema bombycis</i> infecting domestic silkworms <i>Bombyx mori</i> and crop pests <i>Spodoptera litura</i> and <i>Helicoverpa armigera</i>. Our findings reveal that both parasites share a conserved invasion sequence targeting ovariole sheath cells, follicular cells, nurse cells, and ultimately oocytes. Notably, infection of follicular and nurse cells consistently precedes oocyte invasion, suggesting a strategic utilization of these cells for efficient transmission. Contrasting patterns were observed between the two parasites: while <i>N. bombycis</i> exhibits lower infection rates and produces mature spores in both oocytes and nurse cells, <i>N. pernyi</i> displays higher parasite loads with proliferative stages predominant throughout infection. A critical innovation emerges from our RNA interference experiments, where knockdown of host vitellogenin (Vg) significantly reduced microsporidian loads, identifying Vg as a conserved molecular facilitator in TOT. These findings not only elucidate the evolutionary conservation of vertical transmission mechanisms among microsporidia but also pinpoint Vg as a promising target for intervention against these pathogens. This research advances our understanding of vertical transmission of fungal parasites and offers novel avenues for disease control.微孢子虫（Microsporidia）是一类广泛分布的专性细胞内寄生虫，可感染从人类到经济重要性动物在内的多种宿主，其主要垂直传播方式为经卵传递（transovarial transmission, TOT）。尽管经卵传递具有重要生物学意义，但微孢子虫经卵传递的分子机制至今仍未阐明。本研究对两个独立模型系统中的经卵传递过程开展了比较分析：一是侵染野生柞蚕（*Antheraea pernyi*）的柞蚕微孢子虫（*Nosema pernyi*），二是侵染家蚕（*Bombyx mori*）以及农作物害虫斜纹夜蛾（*Spodoptera litura*）、棉铃虫（*Helicoverpa armigera*）的家蚕微孢子虫（*Nosema bombycis*）。 研究结果显示，两种寄生虫均拥有保守的侵袭序列，可靶向卵巢鞘细胞、卵泡细胞、滋养细胞，最终侵染卵母细胞。值得注意的是，对卵泡细胞与滋养细胞的侵染始终早于卵母细胞侵染，这提示两类寄生虫会通过策略性利用这些细胞实现高效传播。 两种寄生虫的侵染模式存在显著差异：家蚕微孢子虫的感染率较低，且可在卵母细胞与滋养细胞中产生成熟孢子；而柞蚕微孢子虫的寄生虫载量更高，且整个侵染过程以增殖阶段为主导。 本研究的RNA干扰（RNA interference, RNAi）实验取得了一项关键发现——宿主卵黄原蛋白（vitellogenin, Vg）的敲低可显著降低微孢子虫的载量，由此确定Vg是经卵传递过程中的保守分子辅助因子。 本研究不仅阐明了微孢子虫垂直传播机制的进化保守性，还确定Vg可作为防控这类病原体的潜在干预靶点。该研究深化了我们对真菌类寄生虫垂直传播的认知，同时为病害防控提供了全新的研究方向。