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

• Published in: Cell reports (Cambridge) Vol. 26; no. 13; pp. 3586 - 3599.e7
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2019; Elsevier
• Subjects: Adult; Aged; AIDS; Animals; biomarker; Cells, Cultured; co-infection; Coinfection - pathology; Coinfection - virology; Female; HIV Infections - complications; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - virology; HIV-1; Humans; IL-10; Immunology; Interleukin-10 - metabolism; Life Sciences; Macaca mulatta; macrophage; Macrophage Activation; Macrophages - pathology; Macrophages - virology; Male; Microbiology and Parasitology; Middle Aged; monocyte; Mycobacterium tuberculosis; Nanotubes; Signal Transduction; STAT3; STAT3 Transcription Factor - metabolism; tuberculosis; Tuberculosis, Pulmonary - complications; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - pathology; tunneling nanotubes; viral spread; Virology; Virus Replication; Young Adult; HIV-1; Mycobacterium tuberculosis; co-infection; tuberculosis; STAT3; AIDS; macrophage; monocyte; tunneling nanotubes; viral spread; biomarker; IL-10; Biomarker; Co-infection; Tuberculosis; Monocyte; Tunneling nanotubes; Viral spread; Macrophage
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.02.091

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. [Display omitted] •TB-induced anti-inflammatory M(IL-10) macrophages are prone to HIV-1 overproduction•Tunneling nanotubes between TB-induced M(IL-10) macrophages promote HIV-1 spread•The IL-10/STAT3 axis triggers tunneling nanotube induction in the TB microenvironment•M(IL-10) macrophages accumulate in TB/HIV co-infected patients and non-human primates 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.