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

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• dc.contributor.author Souriant, Shanti
• dc.contributor.author Lastrucci, Claire
• dc.contributor.author Vérollet, Christel
• dc.date.accessioned 2019-05-20T07:54:59Z
• dc.date.available 2019-05-20T07:54:59Z
• dc.date.issued 2019
• dc.description.abstract 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Souriant S, Balboa L, Dupont M, Pingris K, Kviatcovsky D, Cougoule C et al. Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages. Cell Rep. 2019; 26(13):3586-3599.e7. DOI 10.1016/j.celrep.2019.02.091
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2019.02.091
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/37248
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep. 2019; 26(13):3586-3599.e7
• dc.rights © 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/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword AIDS
• dc.subject.keyword HIV-1
• dc.subject.keyword IL-10
• dc.subject.keyword Mycobacterium tuberculosis
• dc.subject.keyword STAT3
• dc.subject.keyword Biomarker
• dc.subject.keyword Co-infection
• dc.subject.keyword Macrophage
• dc.subject.keyword Monocyte
• dc.subject.keyword Tuberculosis
• dc.subject.keyword Tunneling nanotubes
• dc.subject.keyword Viral spread
• dc.title Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion