CX3CR1(+) mononuclear phagocytes control immunity to intestinal fungi.

CX3CR1(+) mononuclear phagocytes control immunity to intestinal fungi.
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DOI:
10.1126/science.aao1503
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发表时间:
2018-01-12
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Iliev ID
Iliev ID
中科院分区:
其他
文献类型:
--
作者:
Leonardi I;Li X;Semon A;Li D;Doron I;Putzel G;Bar A;Prieto D;Rescigno M;McGovern DPB;Pla J;Iliev ID

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肠道真菌是微生物群的重要组成部分,最近的研究揭示了它们在调节宿主免疫稳态和炎症性疾病方面的潜力。尽管如此,控制肠道菌群免疫的机制仍然未知。我们发现 CX3CR1+ 单核吞噬细胞 (MNP) 对于启动针对肠道真菌的先天和适应性免疫反应至关重要。 CX3CR1+ MNP 表达抗真菌受体并以 Syk 依赖性方式激活抗真菌反应。 CX3CR1+ MNP 的基因消融导致肠道真菌群落发生变化,并导致严重结肠炎,但通过抗真菌治疗可以缓解。 CX3CR1 编码基因的错义突变导致克罗恩病患者的抗真菌反应受损。这些结果揭示了 CX3CR1+ MNP 作为健康和疾病期间肠道菌群与宿主免疫之间相互作用的介质的作用。
Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut mycobiota remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk dependent manner. Genetic ablation of CX3CR1+ MNPs led to changes in the gut fungal communities and to severe colitis that was rescued by antifungal treatment. A missense mutation in the gene encoding CX3CR1 led to impaired antifungal responses in Crohn’s Disease patients. These results unravel the role of CX3CR1+ MNPs as mediators of the interactions between intestinal mycobiota and host immunity during health and disease.
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