Neurturin regulates the lung-resident macrophage inflammatory response to viral infection.
Glial Cell Line-Derived Neurotrophic Factor
/ metabolism
Glial Cell Line-Derived Neurotrophic Factor Receptors
/ metabolism
Humans
Lung
/ immunology
Macrophages
/ immunology
Macrophages, Alveolar
/ immunology
Neurons
/ metabolism
Neurturin
/ metabolism
Proto-Oncogene Proteins c-ret
/ metabolism
RNA, Messenger
/ metabolism
Virus Diseases
/ immunology
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
15
05
2020
revised:
15
09
2020
accepted:
22
09
2020
entrez:
6
10
2020
pubmed:
7
10
2020
medline:
14
7
2021
Statut:
epublish
Résumé
Lung-resident macrophages are crucial to the maintenance of health and in the defence against lower respiratory tract infections. Macrophages adapt to local environmental cues that drive their appropriate function; however, this is often dysregulated in many inflammatory lung pathologies. In mucosal tissues, neuro-immune interactions enable quick and efficient inflammatory responses to pathogenic threats. Although a number of factors that influence the antimicrobial response of lung macrophages are known, the role of neuronal factors is less well understood. Here, we show an intricate circuit involving the neurotrophic factor, neurturin (NRTN) on human lung macrophages that dampens pro-inflammatory cytokine release and modulates the type of matrix metalloproteinases produced in response to viral stimuli. This circuit involves type 1 interferon-induced up-regulation of RET that when combined with the glial cell line-derived neurotrophic factor (GDNF) receptor α2 (GFRα2) allows binding to epithelial-derived NRTN. Our research highlights a non-neuronal immunomodulatory role for NRTN and a novel process leading to a specific antimicrobial immune response by human lung-resident macrophages.
Identifiants
pubmed: 33020210
pii: 3/12/e202000780
doi: 10.26508/lsa.202000780
pmc: PMC7556752
pii:
doi:
Substances chimiques
GDNF protein, human
0
GFRA2 protein, human
0
Glial Cell Line-Derived Neurotrophic Factor
0
Glial Cell Line-Derived Neurotrophic Factor Receptors
0
Neurturin
0
RNA, Messenger
0
Proto-Oncogene Proteins c-ret
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202865/Z/16/Z
Pays : United Kingdom
Informations de copyright
© 2020 Connolly et al.
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