Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
Dupont, Maeva (Université de Toulouse)
Souriant, Shanti (Université de Toulouse)
Balboa, Luciana (Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires)
Vu Manh, Thien-Phong (Aix Marseille Univ, CNRS, INSERM, CIML, Marseille)
Pingris, Karine (Université de Toulouse)
Rousset, Stella (Université de Toulouse)
Cougoule, Céline (Université de Toulouse)
Rombouts, Yoann (Université de Toulouse)
Poincloux, Renaud (Université de Toulouse)
Ben Neji, Myriam (Université de Toulouse)
Allers, Carolina (Tulane University, Covington)
Kaushal, Deepak (Tulane University, Covington)
Kuroda, Marcelo J. (Tulane University, Covington)
Benet, Susana (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez-Picado, Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Izquierdo Useros, Nuria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Sasiain, Maria del Carmen (Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires)
Maridonneau-Parini, Isabelle (Université de Toulouse)
Neyrolles, Olivier (Université de Toulouse)
Vérollet, Christel (Université de Toulouse)
Lugo-Villarino, Geanncarlo (Université de Toulouse)

Fecha:	2020
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	eLife, Vol. 9 (march 2020) , ISSN 2050-084X

DOI: 10.7554/eLife.52535
PMID: 32223897

24 p, 4.1 MB

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