LC3-Associated Phagocytosis Is Required for Dendritic Cell Inflammatory Cytokine Response to Gut Commensal Yeast Saccharomyces cerevisiae.
LC3-Associated Phagocytosis Is Required for Dendritic Cell Inflammatory Cytokine Response to Gut Commensal Yeast Saccharomyces cerevisiae.
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DOI：
10.3389/fimmu.2017.01397
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发表时间：
2017
影响因子：
7.3
通讯作者：
Kawasaki N
中科院分区：
文献类型：
--
作者：
Lamprinaki D;Beasy G;Zhekova A;Wittmann A;James S;Dicks J;Iwakura Y;Saijo S;Wang X;Chow CW;Roberts I;Korcsmaros T;Mayer U;Wileman T;Kawasaki N
被称为真菌菌群的人类真菌微生物群越来越被认为是人类肠道健康和疾病的关键因素。非致病性共生酵母菌，如酿酒酵母菌，促进肠道内稳态，而肠道菌群的生态失调与炎症有关。聚糖结合受体（凝集素）是肠道中宿主-真菌相互作用的关键宿主因子。它们在树突状细胞（dc）等免疫细胞上表达，并识别真菌多糖。这种相互作用对于在肠道中建立适当的免疫反应以及清除真菌病原体是必不可少的。最近的研究表明，微管相关蛋白轻链3 （LC3）相关吞噬（LAP）参与了凝集素与真菌的相互作用。然而，LAP对凝集素功能的生物学影响在很大程度上仍然难以捉摸。在本报告中，我们证明了小鼠LAP与树突状细胞相关的凝集素2 （Dectin-2）有关，这是一种真菌α-甘露聚糖多糖特异性的c型凝集素。我们发现小鼠Dectin-2可以识别共生酵母酿酒酵母和哈萨克斯坦异孢酵母。小鼠骨髓源性dc （bmdc）以Dectin-2和脾酪氨酸激酶（Syk）依赖的方式对酵母产生炎症细胞因子TNFα和IL-1β。我们发现酿酒梭菌和异孢梭菌内化后在小鼠bmdc中诱导LAP。此外，LC3以Dectin-2和syk依赖的方式被酵母刺激BMDCs激活。为了研究LAP对Dectin-2酵母相互作用的生物学影响，我们建立了一种敲入小鼠菌株（Atg16L1E230，之后称为E230）， BMDCs表现出自噬活性和LAP阴性表型。当酵母刺激时，E230 BMDCs产生的TNFα和IL-1β显著减少。综上所述，我们揭示了Dectin-2和LAP之间的一种新的联系，这种联系使宿主免疫细胞能够对真菌群做出反应。
The human fungal microbiota known as mycobiota is increasingly recognized as a critical factor in human gut health and disease. Non-pathogenic commensal yeasts such as Saccharomyces cerevisiae promote homeostasis in the gut, whereas dysbiosis of the gut mycobiota is associated with inflammation. Glycan-binding receptors (lectins) are key host factors in host–mycobiota interaction in the gut. They are expressed on immune cells such as dendritic cells (DCs) and recognize fungal polysaccharides. This interaction is imperative to mount appropriate immune responses for immune homeostasis in the gut as well as clearance of fungal pathogens. Recent studies demonstrate that microtubule-associated protein light-chain 3 (LC3)-associated phagocytosis (LAP) is involved in lectin–fungi interactions. Yet, the biological impact of LAP on the lectin function remains largely elusive. In this report, we demonstrate that in mouse LAP is linked to dendritic cell-associated lectin 2 (Dectin-2), a C-type lectin specific to fungal α-mannan polysaccharide. We found that mouse Dectin-2 recognizes commensal yeast S. cerevisiae and Kazachstania unispora. Mouse bone marrow-derived DCs (BMDCs) produced inflammatory cytokines TNFα and IL-1β in response to the yeasts in a Dectin-2 and spleen tyrosine kinase (Syk)-dependent manner. We found that S. cerevisiae and K. unispora induced LAP in mouse BMDCs upon internalization. Furthermore, LC3 was activated by stimulation of BMDCs with the yeasts in a Dectin-2 and Syk-dependent manner. To address the biological impact of LAP on Dectin-2 yeast interaction, we established a knock-in mouse strain (Atg16L1E230, thereafter called E230), which BMDCs exhibit autophagy-active and LAP-negative phenotypes. When stimulated with yeasts, E230 BMDCs produced significantly less amounts of TNFα and IL-1β. Taken together, we revealed a novel link between Dectin-2 and LAP that enables host immune cells to respond to mycobiota.
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DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Cadwell K
通讯作者：
Cadwell K
非规范自噬抑制自身炎症，类似狼疮的对垂死细胞的反应。
影响因子：
64.8
作者：
Martinez J;Cunha LD;Park S;Yang M;Lu Q;Orchard R;Li QZ;Yan M;Janke L;Guy C;Linkermann A;Virgin HW;Green DR
通讯作者：
Green DR
影响因子：
24.5
作者：
Sokol H;Leducq V;Aschard H;Pham HP;Jegou S;Landman C;Cohen D;Liguori G;Bourrier A;Nion-Larmurier I;Cosnes J;Seksik P;Langella P;Skurnik D;Richard ML;Beaugerie L
通讯作者：
Beaugerie L
DOI：
10.1074/jbc.m117.799080
发表时间：
2017-08-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Feinberg H;Jégouzo SAF;Rex MJ;Drickamer K;Weis WI;Taylor ME
通讯作者：
Taylor ME
影响因子：
32.4
作者：
Saijo, Shinobu;Ikeda, Satoshi;Iwakura, Yoichiro
通讯作者：
Iwakura, Yoichiro