학술논문
Tuberculosis Exacerbates HIV-1 Infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages
Document Type
article
Author
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; del Carmen Sasiain, Maria; Neyrolles, Olivier; Maridonneau-Parini, Isabelle; Lugo-Villarino, Geanncarlo; Vérollet, Christel
Source
Cell Reports. 26(13)
Subject
Language
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.