info:eu-repo/semantics/article
Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
Fecha
2020-03Registro en:
Dupont, Maeva; Souriant, Shanti; Balboa, Luciana; Vu Manh, Thien Phong; Pingris, Karine; et al.; Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages; eLife Sciences Publications Ltd; eLife; 9; 3-2020; 1-39
2050-084X
CONICET Digital
CONICET
Autor
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
Resumen
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 opens new avenues to understand TNT biology.