Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect mucosal surfaces from pathogens or to maintain microbiome homeostasis. To address this central question, we used a primitive vertebrate species (rainbow trout) in which we temporarily depleted its mucosal Ig (sIgT). Fish devoid of sIgT became highly susceptible to a mucosal parasite and failed to develop compensatory IgM responses against it. IgT depletion also induced a profound dysbiosis marked by the loss of sIgT-coated beneficial taxa, expansion of pathobionts, tissue damage, and inflammation. Restitution of sIgT levels in IgT-depleted fish led to a reversal of microbial translocation and tissue damage, as well as to restoration of microbiome homeostasis. Our findings indicate that specialization of sIgs in pathogen and microbiota control occurred concurrently early in evolution, thus revealing primordially conserved principles under which primitive and modern sIgs operate in the control of microbes at mucosal surfaces.

中文翻译：

---

黏膜免疫球蛋白在病原体控制和微生物群稳态中的专业化发生在脊椎动物进化的早期。

尽管哺乳动物分泌型免疫球蛋白A（sIgA）靶向粘膜病原体以消除，但它与微生物群的相互作用也可以实现共生定殖和体内平衡。控制病原体与微生物群的矛盾要求提出了是否发展粘膜（分泌型）Igs（sIgs）的主要目的是保护粘膜表面免受病原体侵害或维持微生物组稳态。为了解决这个核心问题，我们使用了原始的脊椎动物物种（虹鳟鱼），其中我们暂时消耗了其粘膜Ig（sIgT）。缺少sIgT的鱼变得对粘膜寄生虫高度敏感，并且未能对它产生补偿性IgM反应。IgT的消耗也引起了严重的营养不良，其特征是sIgT包被的有益类群的丢失，病原菌的扩张，组织损伤和炎症。消耗IgT的鱼类中sIgT水平的恢复导致微生物易位和组织损伤的逆转，以及微生物组稳态的恢复。我们的发现表明，在病原体和微生物群控制中sIg的专业化在进化的早期同时发生，因此揭示了原始和现代sIg在黏膜表面控制微生物的原始保守原理。