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

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

eLife

eLife Sciences Publications, Ltd., 2012-

Lugar: Cambridge; 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.