학술논문
Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
Document Type
article
Author
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 Martinez-Picado; Nuria Izquierdo-Useros; Maria del Carmen Sasiain; Isabelle Maridonneau-Parini; Olivier Neyrolles; Christel Vérollet; Geanncarlo Lugo-Villarino
Source
eLife, Vol 9 (2020)
Subject
Language
English
ISSN
2050-084X
Abstract
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.