Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages

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...

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Detalles Bibliográficos
Autores: Souriant, Shanti, Lastrucci, Claire, Vérollet, Christel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/37248
Acceso en línea:http://hdl.handle.net/10230/37248
http://dx.doi.org/10.1016/j.celrep.2019.02.091
Access Level:acceso abierto
Palabra clave:AIDS
HIV-1
IL-10
Mycobacterium tuberculosis
STAT3
Biomarker
Co-infection
Macrophage
Monocyte
Tuberculosis
Tunneling nanotubes
Viral spread
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spelling Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophagesSouriant, ShantiLastrucci, ClaireVérollet, ChristelAIDSHIV-1IL-10Mycobacterium tuberculosisSTAT3BiomarkerCo-infectionMacrophageMonocyteTuberculosisTunneling nanotubesViral spreadThe 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.Elsevier201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/37248http://dx.doi.org/10.1016/j.celrep.2019.02.091reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCell Rep. 2019; 26(13):3586-3599.e7© 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/372482026-06-12T07:21:37Z
dc.title.none.fl_str_mv Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
title Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
spellingShingle Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
Souriant, Shanti
AIDS
HIV-1
IL-10
Mycobacterium tuberculosis
STAT3
Biomarker
Co-infection
Macrophage
Monocyte
Tuberculosis
Tunneling nanotubes
Viral spread
title_short Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
title_full Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
title_fullStr Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
title_full_unstemmed Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
title_sort Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
dc.creator.none.fl_str_mv Souriant, Shanti
Lastrucci, Claire
Vérollet, Christel
author Souriant, Shanti
author_facet Souriant, Shanti
Lastrucci, Claire
Vérollet, Christel
author_role author
author2 Lastrucci, Claire
Vérollet, Christel
author2_role author
author
dc.subject.none.fl_str_mv AIDS
HIV-1
IL-10
Mycobacterium tuberculosis
STAT3
Biomarker
Co-infection
Macrophage
Monocyte
Tuberculosis
Tunneling nanotubes
Viral spread
topic AIDS
HIV-1
IL-10
Mycobacterium tuberculosis
STAT3
Biomarker
Co-infection
Macrophage
Monocyte
Tuberculosis
Tunneling nanotubes
Viral spread
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/37248
http://dx.doi.org/10.1016/j.celrep.2019.02.091
url http://hdl.handle.net/10230/37248
http://dx.doi.org/10.1016/j.celrep.2019.02.091
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Rep. 2019; 26(13):3586-3599.e7
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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