Pathogenic fungi reside in the intestinal microbiota but rarely cause disease. Little is known about the interactions between fungi and the immune system that promote commensalism. Here we investigate the role of adaptive immunity in promoting mutual interactions between fungi and host. We find that potentially pathogenic Candida species induce and are targeted by intestinal immunoglobulin A (IgA) responses. Focused studies on Candida albicans reveal that the pathogenic hyphal morphotype, which is specialized for adhesion and invasion, is preferentially targeted and suppressed by intestinal IgA responses. IgA from mice and humans directly targets hyphal-enriched cell-surface adhesins. Although typically required for pathogenesis, C. albicans hyphae are less fit for gut colonization^1,2 and we show that immune selection against hyphae improves the competitive fitness of C. albicans. C. albicans exacerbates intestinal colitis³ and we demonstrate that hyphae and an IgA-targeted adhesin exacerbate intestinal damage. Finally, using a clinically relevant vaccine to induce an adhesin-specific immune response protects mice from C. albicans-associated damage during colitis. Together, our findings show that adaptive immunity suppresses harmful fungal effectors, with benefits to both C. albicans and its host. Thus, IgA uniquely uncouples colonization from pathogenesis in commensal fungi to promote homeostasis.

致病真菌存在于肠道微生物群中，但很少引起疾病。人们对真菌与促进共生的免疫系统之间的相互作用知之甚少。在这里，我们研究适应性免疫在促进真菌和宿主之间的相互作用中的作用。我们发现潜在的致病性念珠菌属物种诱导肠道免疫球蛋白 A (IgA) 反应并被其靶向。对白色念珠菌的重点研究表明，专门用于粘附和入侵的致病性菌丝形态型优先被肠道 IgA 反应靶向和抑制。来自小鼠和人类的 IgA 直接靶向富含菌丝的细胞表面粘附素。虽然通常是发病机制所必需的，但白色念珠菌菌丝不太适合肠道定植^1,2并且我们表明针对菌丝的免疫选择提高了白色念珠菌的竞争适应性。白色念珠菌会加剧肠道结肠炎³并且我们证明菌丝和 IgA 靶向粘附素会加剧肠道损伤。最后，使用临床相关疫苗诱导粘附素特异性免疫反应可保护小鼠在结肠炎期间免受白色念珠菌相关损伤。总之，我们的研究结果表明适应性免疫抑制有害的真菌效应物，对白色念珠菌及其宿主都有好处。因此，IgA 以独特的方式将共生真菌的定植与发病机制分开，以促进体内平衡。