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

BALBOA, LUCIANA; ROUSSET, STELLA; POINCLOUX, RENAUD; KAUSHAL, DEEPAK; MARTINEZ-PICADO, JAVIER; MARIDONNEAU-PARINI, ISABELLE; LUGO-VILLARINO, GEANNCARLO; DUPONT, MAEVA; MANH, THIEN-PHONG VU; COUGOULE, CÉLINE; NEJI, MYRIAM BEN; KURODA, MARCELO J.; IZQUIERDO-USEROS, NURIA; NEYROLLES, OLIVIER; SOURIANT, SHANTI; PINGRIS, KARINE; ROMBOUTS, YOANN; ALLERS, CAROLINA; BENET, SUSANA; SASIAIN, MARIA DEL CARMEN; VÉROLLET, CHRISTEL

eLife

eLife Sciences Publications Ltd

Año: 2020 vol. 9

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.