Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity.,Cell

当前位置： X-MOL 学术 › Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity.
Cell ( IF 45.5 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.cell.2019.12.016
Abigail Jarret ₁ , Ruaidhrí Jackson ₁ , Coco Duizer ₁ , Marc E Healy ₂ , Jun Zhao ₃ , Joseph M Rone ₄ , Piotr Bielecki ₁ , Esen Sefik ₁ , Manolis Roulis ₁ , Tyler Rice ₁ , Kisha N Sivanathan ₄ , Ting Zhou ₁ , Angel G Solis ₁ , Hanna Honcharova-Biletska ₅ , Karelia Vélez ₆ , Saskia Hartner ₇ , Jun Siong Low ₁ , Rihao Qu ₈ , Marcel R de Zoete ₉ , Noah W Palm ₁ , Aaron M Ring ₁ , Achim Weber ₂ , Andreas E Moor ₆ , Yuval Kluger ₁₀ , Roni Nowarski ₄ , Richard A Flavell ₁₁

Affiliation

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich 8091, Switzerland; Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA.
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; University of Vienna, Universitätsring 1, Wien 1010, Austria.
Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA.
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA; Applied Mathematics Program, Yale University, New Haven, CT 06511, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.

Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium, here, we show that the enteric nervous system (ENS) plays an essential and non-redundant role in governing the antimicrobial protein (AMP) response. Using confocal microscopy and single-molecule fluorescence in situ mRNA hybridization (smFISH) studies, we observed that intestinal neurons produce the pleiotropic cytokine IL-18. Strikingly, deletion of IL-18 from the enteric neurons alone, but not immune or epithelial cells, rendered mice susceptible to invasive Salmonella typhimurium (S.t.) infection. Mechanistically, unbiased RNA sequencing and single-cell sequencing revealed that enteric neuronal IL-18 is specifically required for homeostatic goblet cell AMP production. Together, we show that neuron-derived IL-18 signaling controls tissue-wide intestinal immunity and has profound consequences on the mucosal barrier and invasive bacterial killing.

中文翻译：

肠神经系统衍生的 IL-18 协调粘膜屏障免疫。

粘膜屏障免疫对于维持共生微生物群和对抗侵入性细菌感染至关重要。尽管免疫细胞和上皮细胞被认为是这种复杂平衡的典型协调者，但在这里，我们表明肠神经系统（ENS）在控制抗菌蛋白（AMP）反应中发挥着重要且非冗余的作用。使用共聚焦显微镜和单分子荧光原位 mRNA 杂交 (smFISH) 研究，我们观察到肠道神经元产生多效细胞因子 IL-18。引人注目的是，仅从肠神经元中删除 IL-18，而不是从免疫细胞或上皮细胞中删除 IL-18，会使小鼠容易受到侵袭性鼠伤寒沙门氏菌 (St) 感染。从机制上讲，无偏 RNA 测序和单细胞测序表明，肠神经元 IL-18 是稳态杯状细胞 AMP 产生所特别需要的。我们共同证明，神经元衍生的 IL-18 信号传导控制着组织范围的肠道免疫，并对粘膜屏障和侵袭性细菌杀灭具有深远的影响。

更新日期：2020-01-09

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11