Alveolar macrophage-derived extracellular vesicles inhibit endosomal fusion of influenza virus.
alveolar macrophage
endosome fusion
epithelial cell
extracellular vesicles
influenza
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
17 08 2020
17 08 2020
Historique:
received:
19
03
2020
revised:
05
06
2020
accepted:
15
06
2020
pubmed:
10
7
2020
medline:
7
4
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
Alveolar macrophages (AMs) and epithelial cells (ECs) are the lone resident lung cells positioned to respond to pathogens at early stages of infection. Extracellular vesicles (EVs) are important vectors of paracrine signaling implicated in a range of (patho)physiologic contexts. Here we demonstrate that AMs, but not ECs, constitutively secrete paracrine activity localized to EVs which inhibits influenza infection of ECs in vitro and in vivo. AMs exposed to cigarette smoke extract lost the inhibitory activity of their secreted EVs. Influenza strains varied in their susceptibility to inhibition by AM-EVs. Only those exhibiting early endosomal escape and high pH of fusion were inhibited via a reduction in endosomal pH. By contrast, strains exhibiting later endosomal escape and lower fusion pH proved resistant to inhibition. These results extend our understanding of how resident AMs participate in host defense and have broader implications in the defense and treatment of pathogens internalized within endosomes.
Identifiants
pubmed: 32643835
doi: 10.15252/embj.2020105057
pmc: PMC7429743
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e105057Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM131720
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI140618
Pays : United States
Organisme : American Thoracic Society (ATS)
Organisme : NHLBI NIH HHS
ID : R35 HL144979
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119682
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI117229
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125555
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL149051
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL144481
Pays : United States
Informations de copyright
© 2020 The Authors.
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