Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity.
Animals
Cytokines
/ immunology
Enteric Nervous System
/ immunology
Epithelial Cells
/ immunology
Female
Goblet Cells
/ immunology
Immunity, Mucosal
/ immunology
Interleukin-18
/ biosynthesis
Intestinal Mucosa
/ immunology
Intestine, Small
/ immunology
Male
Mice
Mice, Inbred C57BL
Neurons
/ immunology
Rats
Rats, Sprague-Dawley
Salmonella Infections
/ immunology
Salmonella typhimurium
/ immunology
Signal Transduction
/ immunology
Salmonella
antimicrobial proteins
barrier immunity
colon
goblet cell
homeostasis
inflammasome
microbiota
mucosal immunology
neuroimmunology
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
09 01 2020
09 01 2020
Historique:
received:
15
02
2019
revised:
01
11
2019
accepted:
12
12
2019
entrez:
11
1
2020
pubmed:
11
1
2020
medline:
22
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31923399
pii: S0092-8674(19)31378-9
doi: 10.1016/j.cell.2019.12.016
pmc: PMC7339937
mid: NIHMS1569457
pii:
doi:
Substances chimiques
Cytokines
0
Interleukin-18
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
50-63.e12Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM131642
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIH HHS
ID : S10 OD018521
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008383
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM135928
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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