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

Maeva Dupont (1) , Shanti Souriant (1) , Luciana Balboa (2) , Thien-Phong Vu Manh (3) , Karine Pingris (1) , Stella Rousset (1) , Céline Cougoule (1) , Yoann Rombouts (1) , Renaud Poincloux (1) , Myriam Ben Neji (1) , Carolina Allers (4) , Deepak Kaushal (4) , Marcelo Kuroda (4) , Susana Benet (5, 6) , Javier Martinez-Picado (7, 6) , Nuria Izquierdo-Useros (6) , Maria del Carmen Sasiain (2) , Isabelle Maridonneau-Parini (1) , Olivier Neyrolles (1) , Christel Vérollet (1) , Geanncarlo Lugo-Villarino (1)

1 IPBS - Institut de pharmacologie et de biologie structurale
2 LIA IM-TB/HIV - Immunometabolism and Macrophages in Tuberculosis/Human Immunodeficiency Virus-1 Co-infection
3 CIML - Centre d'Immunologie de Marseille - Luminy
4 Tulane National Primate Research Center
5 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
6 IrsiCaixa (Institut de Recerca de la Sida)
7 Open University of Catalonia [Barcelona]

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 upregulation 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

Domaines: Sciences du Vivant [q-bio]

Maeva Dupont, Shanti Souriant, Luciana Balboa, Thien-Phong Vu Manh, Karine Pingris, et al.. Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages. eLife, 2020, 9, ⟨10.7554/eLife.52535⟩. ⟨hal-02995702⟩