Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages

• Published in: eLife Vol. 9
• Main Authors: Dupont, Maeva, Souriant, Shanti, Balboa, Luciana, Vu Manh, Thien-Phong, Pingris, Karine, Rousset, Stella, Cougoule, Céline, Rombouts, Yoann, Poincloux, Renaud, Ben Neji, Myriam, Allers, Carolina, Kaushal, Deepak, Kuroda, Marcelo J, Benet, Susana, Martinez-Picado, Javier, Izquierdo-Useros, Nuria, Sasiain, Maria del Carmen, Maridonneau-Parini, Isabelle, Neyrolles, Olivier, Vérollet, Christel, Lugo-Villarino, Geanncarlo
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 30.03.2020; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Alveoli; Animals; Binding sites; Biopsy; Cell Biology; Cells, Cultured; co-infection; Coinfection - immunology; Female; Gene expression; Gene Expression Profiling; HIV; HIV Infections; HIV-1 - pathogenicity; Human immunodeficiency virus; Humans; Infections; Interferon; Interferon Type I - immunology; interferons; Life Sciences; Lymphocytes; Macaca mulatta; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - virology; Male; Microbiology and Infectious Disease; Microenvironments; mycobacterium tuberculosis; Nanotubes; Pathogenesis; Risk factors; Sialic Acid Binding Ig-like Lectin 1 - genetics; Sialic Acid Binding Ig-like Lectin 1 - immunology; Stat1 protein; Tuberculosis; Tuberculosis, Pulmonary - immunology; tunneling natotubes; macrophages; rhesus macaque; cell biology; interferons; HIV; co-infection; infectious disease; microbiology; tunneling natotubes; mycobacterium tuberculosis; human
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.52535

While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by which Mycobacterium tuberculosis (Mtb) worsens HIV-1 pathogenesis remain scarce. We showed that HIV-1 infection is exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of Siglec-1 receptor. Siglec-1 expression depends on Mtb-induced production of type I interferon (IFN-I). In co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of IFN-I/STAT1 pathway. Siglec-1 localizes mainly on microtubule-containing TNT that are long and carry HIV-1 cargo. Siglec-1 depletion decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer, and abrogates the exacerbation of HIV-1 infection induced by Mtb. Altogether, we uncover a deleterious role for Siglec-1 in TB-HIV-1 co-infection and open new avenues to understand TNT biology.