Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
Maeva Dupont, Shanti Souriant, Luciana Balboa, Thien‐Phong Vu Manh, Karine Pingris, Stella Rousset, Céline Cougoule, Yoann Rombouts, Renaud Poincloux, Myriam Ben Neji, Carolina Allers, Deepak Kaushal, Marcelo J. Kuroda, Susana Benet, Javier Martínez‐Picado, Nuria Izquierdo‐Useros, Marı́a del Carmen Sasiain, Isabelle Maridonneau‐Parini, Olivier Neyrolles, Christel Vérollet, Geanncarlo Lugo‐Villarino
Abstract
(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.