Tuberculosis Exacerbates HIV-1 Infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages.
Adult
Aged
Animals
Cells, Cultured
Coinfection
/ pathology
Female
HIV Infections
/ complications
Humans
Interleukin-10
/ metabolism
Macaca mulatta
Macrophage Activation
Macrophages
/ pathology
Male
Middle Aged
Mycobacterium tuberculosis
Nanotubes
STAT3 Transcription Factor
/ metabolism
Signal Transduction
Tuberculosis, Pulmonary
/ complications
Virus Replication
Young Adult
AIDS
HIV-1
IL-10
Mycobacterium tuberculosis
STAT3
biomarker
co-infection
macrophage
monocyte
tuberculosis
tunneling nanotubes
viral spread
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 03 2019
26 03 2019
Historique:
received:
23
08
2018
revised:
08
12
2018
accepted:
21
02
2019
entrez:
28
3
2019
pubmed:
28
3
2019
medline:
21
5
2020
Statut:
ppublish
Résumé
The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironment, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity. Furthermore, HIV-1/Mtb co-infected patients display an accumulation of M(IL-10) macrophage markers (soluble CD163 and MerTK). These M(IL-10) macrophages form direct cell-to-cell bridges, which we identified as tunneling nanotubes (TNTs) involved in viral transfer. TNT formation requires the IL-10/STAT3 signaling pathway, and targeted inhibition of TNTs substantially reduces the enhancement of HIV-1 cell-to-cell transfer and overproduction in M(IL-10) macrophages. Our study reveals that TNTs facilitate viral transfer and amplification, thereby promoting TNT formation as a mechanism to be explored in TB/AIDS potential therapeutics.
Identifiants
pubmed: 30917314
pii: S2211-1247(19)30277-3
doi: 10.1016/j.celrep.2019.02.091
pmc: PMC6733268
mid: NIHMS1044115
pii:
doi:
Substances chimiques
IL10 protein, human
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3586-3599.e7Subventions
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI097059
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI110163
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI110163
Pays : United States
Organisme : NIAID NIH HHS
ID : UC6 AI058609
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.