Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells.
CP: Microbiology
HIV-1
HIV-associated co-morbidities
Nef
cholesterol biosynthesis
extracellular vesicles
inflammation
lipid rafts
monocyte-derived macrophages
trained immunity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
22 11 2022
22 11 2022
Historique:
received:
04
05
2022
revised:
31
08
2022
accepted:
25
10
2022
entrez:
23
11
2022
pubmed:
24
11
2022
medline:
26
11
2022
Statut:
ppublish
Résumé
A possible explanation for chronic inflammation in HIV-infected individuals treated with anti-retroviral therapy is hyperreactivity of myeloid cells due to a phenomenon called "trained immunity." Here, we demonstrate that human monocyte-derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, release increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect is associated with chromatin changes at the genes involved in inflammation and cholesterol metabolism pathways and upregulation of the lipid rafts and is blocked by methyl-β-cyclodextrin, statin, and an inhibitor of the lipid raft-associated receptor IGF1R. Bone-marrow-derived macrophages from exNef-injected mice, as well as from mice transplanted with bone marrow from exNef-injected animals, produce elevated levels of tumor necrosis factor α (TNF-α) upon stimulation. These phenomena are consistent with exNef-induced trained immunity that may contribute to persistent inflammation and associated co-morbidities in HIV-infected individuals with undetectable HIV load.
Identifiants
pubmed: 36417867
pii: S2211-1247(22)01548-0
doi: 10.1016/j.celrep.2022.111674
pmc: PMC9733434
mid: NIHMS1852524
pii:
doi:
Substances chimiques
nef Gene Products, Human Immunodeficiency Virus
0
nef protein, Human immunodeficiency virus 2
0
nef protein, Human immunodeficiency virus 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
111674Subventions
Organisme : NIAID NIH HHS
ID : P30 AI087714
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL158305
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL140977
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI117970
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI172028
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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