Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173963/
https://www.ncbi.nlm.nih.gov/pubmed/32223897
http://dx.doi.org/10.7554/eLife.52535
Descripción
Sumario: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.