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

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

Cell (2020-01-11)
Abigail Jarret, Ruaidhrí Jackson, Coco Duizer, Marc E Healy, Jun Zhao, Joseph M Rone, Piotr Bielecki, Esen Sefik, Manolis Roulis, Tyler Rice, Kisha N Sivanathan, Ting Zhou, Angel G Solis, Hanna Honcharova-Biletska, Karelia Vélez, Saskia Hartner, Jun Siong Low, Rihao Qu, Marcel R de Zoete, Noah W Palm, Aaron M Ring, Achim Weber, Andreas E Moor, Yuval Kluger, Roni Nowarski, Richard A Flavell
摘要

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.

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Sigma-Aldrich
分散酶®II, protease
Sigma-Aldrich
胶原酶 来源于溶组织梭菌, Type XI, 2-5 FALGPA units/mg solid, ≥800 CDU/mg solid
Sigma-Aldrich
脱氧核糖核酸酶II 来源于牛脾脏, Type V, essentially salt-free, lyophilized powder, ≥1,000 units/mg protein