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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Jan 11

PMID 31923399

Citations 77

Authors

Abigail Jarret

Ruaidhri 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 Velez

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

Affiliations

Soon will be listed here.

Abstract

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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