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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Detalhes bibliográficos
Autores: Souriant, Shanti, Balboa, Luciana, Dupont, Maeva, Pingris, Karine, Kviatcovsky, Denise, Cougoule, Céline, Lastrucci, Claire, Bah, Aicha, Gasser, Romain, Poincloux, Renaud, Raynaud Messina, Brigitte, Al Saati, Talal, Inwentarz, Sandra, Poggi, Susana, Moraña, Eduardo Jose, González Montaner, Pablo, Corti, Marcelo, Lagane, Bernard, Vergne, Isabelle, Allers, Carolina, Kaushal, Deepak, Kuroda, Marcelo J., Sasiain, Maria del Carmen, Neyrolles, Olivier, Maridonneau Parini, Isabelle, Lugo Villarino, Geanncarlo, Vérollet, Christel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/183500
Acesso em linha:http://hdl.handle.net/11336/183500
Access Level:acceso abierto
Palavra-chave:AIDS
BIOMARKER
CO-INFECTION
HIV-1
IL-10
MACROPHAGE
MONOCYTE
MYCOBACTERIUM TUBERCULOSIS
STAT3
TUBERCULOSIS
TUNNELING NANOTUBES
VIRAL SPREAD
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo: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. Tuberculosis is a clear, yet confounding, risk factor for HIV-1-induced morbidity and mortality. In this issue, Souriant et al. reveal that a tuberculosis-associated microenvironment triggers IL-10/STAT3-dependent tunneling nanotube formation in M(IL-10) macrophages, which promotes HIV-1 exacerbation during co-infection. M(IL-10) macrophage accumulation is also observed in vivo in co-infected subjects.

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