Cell:肠道真菌如何塑造抗真菌免疫?
创作:mildbreeze 审核:mildbreeze 03月01日
  • 健康人和小鼠中,相当比例的肠道共生真菌(尤其是念珠菌属)能被血清中的抗真菌IgG识别,肠道中的白色念珠菌是这类抗体的主要诱导者;
  • 小鼠试验表明,肠道的真菌定植能引起肠外(脾脏)淋巴组织生发中心B细胞扩增,产生的抗真菌IgG可抵抗正常甚至免疫抑制状态下的多种念珠菌感染;
  • 抗真菌IgG的生成依赖于先天免疫调控因子CARD9和CARD9+CX3CR1+巨噬细胞,在侵袭性念珠菌病患者中CARD9功能缺失性基因突变与抗真菌IgG应答缺陷相关。
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mildbreeze
自然感染和接种疫苗,能通过诱导特异性的抗体,发挥对特定病毒和细菌病原体的免疫作用,但是目前针对真菌病原体的疫苗和中和抗体疗法还非常缺乏。Cell发表的一项最新研究发现,肠道真菌群在诱导宿主的抗真菌IgG抗体免疫中发挥关键作用。该研究表明肠道中的真菌(比如白色念珠菌)能通过CX3CR1+巨噬细胞的CARD9信号,引起肠外淋巴组织中的生发中心B细胞扩增,以产生抗真菌IgG,从而保护宿主抵抗致命的系统性真菌感染。这些发现对于研发抗真菌的疫苗和抗体有重要意义。
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Cell [IF:38.637]

Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies

人肠道真菌群通过CARD9依赖性的抗真菌IgG抗体的诱导作用调节免疫

10.1016/j.cell.2021.01.016

02-05, Article

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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.

First Authors:
Itai Doron

Correspondence Authors:
Iliyan D Iliev

All Authors:
Itai Doron,Irina Leonardi,Xin V Li,William D Fiers,Alexa Semon,Meghan Bialt-DeCelie,Mélanie Migaud,Iris H Gao,Woan-Yu Lin,Takato Kusakabe,Anne Puel,Iliyan D Iliev

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ScienceDaily新闻网站

Fungi in the gut prime immunity against infection

2021-02-05

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