Tuberculosis Exacerbates HIV-1 infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages

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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 | Sasiain, Maria del Carmen | Neyrolles, Olivier | Maridonneau-Parini, Isabelle | Lugo-Villarino, Geanncarlo | Vérollet, Christel

Edité par CCSD ; Elsevier Inc -

International audience. 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 microenvironments, 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. Further, 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.

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