Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides.

Acetylcholine / immunology Animals Bacterial Proteins / immunology Biological Transport Cilia / drug effects Female Formates / metabolism Gene Expression Humans Immunity, Innate Male Mice Mice, Inbred C57BL Mice, Knockout Mucociliary Clearance / immunology Optogenetics / methods Paracrine Communication / immunology Pulmonary Disease, Chronic Obstructive / genetics Receptor, Muscarinic M3 / genetics Receptors, G-Protein-Coupled / genetics TRPM Cation Channels / deficiency Taste Buds / immunology Trachea / drug effects Virulence

acetylcholine bitter receptors brush cells chemosensory cells formyl peptide receptors formylated bacterial peptides mucociliary clearance taste transduction trachea transient receptor potential cation channel subfamily M member 5 tuft cells

Journal

Immunity

ISSN: 1097-4180

Titre abrégé: Immunity

Pays: United States

ID NLM: 9432918

Informations de publication

Date de publication:
14 04 2020

Historique:

received: 03 03 2019

revised: 25 12 2019

accepted: 13 03 2020

entrez: 16 4 2020

pubmed: 16 4 2020

medline: 5 11 2020

Statut: ppublish

Résumé

Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense.

Identifiants

DOI: 10.1016/j.immuni.2020.03.005 PMID: 32294408

pubmed: 32294408

pii: S1074-7613(20)30118-7

doi: 10.1016/j.immuni.2020.03.005

pii:

doi:

Substances chimiques

Bacterial Proteins 0

Formates 0

Receptor, Muscarinic M3 0

Receptors, G-Protein-Coupled 0

TRPM Cation Channels 0

Trpm5 protein, mouse 0

oxomethylium 17030-74-9

Acetylcholine N9YNS0M02X

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

683-699.e11

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.