Adaptive immunity induces mutualism between commensal eukaryotes.
Adaptive immunity induces mutualism between commensal eukaryotes.
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DOI：
10.1038/s41586-021-03722-w
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发表时间：
2021-08
期刊：
影响因子：
64.8
通讯作者：
Round JL
中科院分区：
文献类型：
--
作者：
Ost KS;O'Meara TR;Stephens WZ;Chiaro T;Zhou H;Penman J;Bell R;Catanzaro JR;Song D;Singh S;Call DH;Hwang-Wong E;Hanson KE;Valentine JF;Christensen KA;O'Connell RM;Cormack B;Ibrahim AS;Palm NW;Noble SM;Round JL
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相互作用中的作用。我们发现潜在致病性念珠菌会诱导肠道免疫球蛋白 A (IgA) 反应，并成为其目标。对白色念珠菌的集中研究表明，专门用于粘附和侵袭的致病菌丝形态类型优先被肠道 IgA 反应所靶向和抑制。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。尽管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，我们表明针对菌丝的免疫选择可以提高白色念珠菌的竞争适应性。白色念珠菌会加剧肠道结肠炎，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以保护小鼠在结肠炎期间免受白色念珠菌相关的损害。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 独特地将共生真菌中的定植与发病机制分开，以促进体内平衡。
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 and we show that immune selection against hyphae improves the competitive fitness of C. albicans. C. albicans exacerbates intestinal colitis 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.
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影响因子：
30.3
作者：
Kubinak JL;Petersen C;Stephens WZ;Soto R;Bake E;O'Connell RM;Round JL
通讯作者：
Round JL
机会性病原体念珠菌中基因组变异的模式表明，交配的存在和与人类的二次关联。
DOI：
10.1016/j.cub.2017.11.027
发表时间：
2018-01-08
期刊：
Current biology : CB
影响因子：
--
作者：
Carreté L;Ksiezopolska E;Pegueroles C;Gómez-Molero E;Saus E;Iraola-Guzmán S;Loska D;Bader O;Fairhead C;Gabaldón T
通讯作者：
Gabaldón T
影响因子：
7.3
作者：
Millet N;Solis NV;Swidergall M
通讯作者：
Swidergall M
影响因子：
3.6
作者：
Askew, Christopher;Sellam, Adnane;Whiteway, Malcolm
通讯作者：
Whiteway, Malcolm
影响因子：
4.3
作者：
Bai, Xiao-Dong;Liu, Xian-Hua;Tong, Qing-Ying
通讯作者：
Tong, Qing-Ying