免疫系统
免疫学
免疫球蛋白E
模式识别受体
获得性免疫系统
抗原
作者
Itai Doron,Irina Leonardi,Xin Li,William D. Fiers,Alexa Semon,Meghan Bialt-DeCelie,Mélanie Migaud,Iris H. Gao,Woan-Yu Lin,Takato Kusakabe,Anne Puel,Iliyan D. Iliev
出处
期刊:Cell
[Elsevier]
日期:2021-02-18
卷期号:184 (4)
被引量:31
标识
DOI:10.1016/j.cell.2021.01.016
摘要
Summary Antibodies mediate natural and vaccine-induced immunity against viral and bacterial pathogens, whereas fungi represent a widespread kingdom of pathogenic species for which neither vaccine nor neutralizing antibody therapies are clinically available. Here, using a multi-kingdom antibody profiling (multiKAP) approach, we explore the human antibody repertoires against gut commensal fungi (mycobiota). We identify species preferentially targeted by systemic antibodies in humans, with Candida albicans being the major inducer of antifungal immunoglobulin G (IgG). Fungal colonization of the gut induces germinal center (GC)-dependent B cell expansion in extraintestinal lymphoid tissues and generates systemic antibodies that confer protection against disseminated C. albicans or C. auris infection. Antifungal IgG production depends on the innate immunity regulator CARD9 and CARD9+CX3CR1+ macrophages. In individuals with invasive candidiasis, loss-of-function mutations in CARD9 are associated with impaired antifungal IgG responses. These results reveal an important role of gut commensal fungi in shaping the human antibody repertoire through CARD9-dependent induction of host-protective antifungal IgG.
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