Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides
2020-04-14
发表期刊IMMUNITY (IF:25.5[JCR-2023],33.2[5-Year])
ISSN1074-7613
EISSN1097-4180
卷号52期号:4页码:683-+
发表状态已发表
DOI10.1016/j.immuni.2020.03.005
摘要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.
收录类别SCI ; SCIE
语种英语
资助项目German Center for Lung Research (DZL)[ALI-1.1] ; German Center for Lung Research (DZL)[FKZ 82DZL0003A4] ; German Center for Lung Research (DZL)[PH-2.7]
WOS研究方向Immunology
WOS类目Immunology
WOS记录号WOS:000526782600012
出版者CELL PRESS
WOS关键词COMMUNITY-ACQUIRED PNEUMONIA ; NITRIC-OXIDE ; BITTER TASTE ; BORDETELLA-PSEUDOHINZII ; TRANSGENIC MICE ; MOUSE NASAL ; RECEPTORS ; VOMERONASAL ; IMMUNE ; EPITHELIUM
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119452
专题免疫化学研究所_PI研究组_Katsuhiko Mikoshiba组
通讯作者Kummer, Wolfgang
作者单位
1.Justus Liebig Univ, Inst Anat & Cell Biol, German Ctr Lung Res, D-35385 Giessen, Germany
2.Max Planck Inst Heart & Lung Res, Dept Pharmacol, D-61231 Bad Nauheim, Germany
3.Univ Med Ctr Hamburg Eppendorf, Dept Med 3, D-20251 Hamburg, Germany
4.Univ Saarland, Ctr Integrat Physiol & Mol Med, D-66421 Homburg, Germany
5.Philipps Univ, Inst Anat & Cell Biol, D-35037 Marburg, Germany
6.Justus Liebig Univ, Inst Biochem, D-35385 Giessen, Germany
7.Saarland Univ, Ctr Mol Signaling PZMS, Expt Pharmacol, D-66421 Homburg, Germany
8.Justus Liebig Univ, Inst Med Microbiol, German Ctr Infect Res, D-35385 Giessen, Germany
9.Justus Liebig Univ, Inst Hyg & Infect Dis Anim, D-35392 Giessen, Germany
10.Justus Liebig Univ, Dept Internal Med, German Ctr Lung Res, Ctr Interstitial & Rare Lung Dis, D-35385 Giessen, Germany
11.Agaples Lung Clin Waldhof Elgershausen, D-35753 Greifenstein, Germany
12.Ludwig Maximilians Univ Munchen, Walther Straub Inst Pharmacol & Toxicol, German Ctr Lung Res, D-80336 Munich, Germany
13.Philipps Univ, Inst Physiol & Pathophysiol, D-35037 Marburg, Germany
14.Goethe Univ Frankfurt, Dept Pharmacol & Clin Pharm, FB14, D-60438 Frankfurt, Germany
15.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Lab Cell Calcium Signaling, Shanghai 201210, Peoples R China
16.Univ Appl Sci, Dept Informat & Microsyst Technol, D-67659 Kaiserslautern, Germany
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Perniss, Alexander,Liu, Shuya,Boonen, Brett,et al. Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides[J]. IMMUNITY,2020,52(4):683-+.
APA Perniss, Alexander.,Liu, Shuya.,Boonen, Brett.,Keshavarz, Maryam.,Ruppert, Anna-Lena.,...&Kummer, Wolfgang.(2020).Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides.IMMUNITY,52(4),683-+.
MLA Perniss, Alexander,et al."Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides".IMMUNITY 52.4(2020):683-+.
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