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

Autor:	Dupont M; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France., Souriant S; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France., Balboa L; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France.; Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina., Vu Manh TP; Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France., Pingris K; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Rousset S; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Cougoule C; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France., Rombouts Y; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Poincloux R; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Ben Neji M; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Allers C; Tulane National Primate Research Center, Department of Microbiology and Immunology, School of Medicine, Tulane University, Covington, United States., Kaushal D; Tulane National Primate Research Center, Department of Microbiology and Immunology, School of Medicine, Tulane University, Covington, United States., Kuroda MJ; Tulane National Primate Research Center, Department of Microbiology and Immunology, School of Medicine, Tulane University, Covington, United States., Benet S; IrsiCaixa AIDS Research Institute, Department of Retrovirology, Badalona, Spain.; Universitat Autònoma de Barcelona, Barcelona, Spain., Martinez-Picado J; IrsiCaixa AIDS Research Institute, Department of Retrovirology, Badalona, Spain.; University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain., Izquierdo-Useros N; IrsiCaixa AIDS Research Institute, Department of Retrovirology, Badalona, Spain.; Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain., Sasiain MDC; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France.; Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina., Maridonneau-Parini I; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France., Neyrolles O; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France., Vérollet C; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France., Lugo-Villarino G; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.; International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Mar 30; Vol. 9. Date of Electronic Publication: 2020 Mar 30.
DOI:	10.7554/eLife.52535
Abstrakt:	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. Competing Interests: MD, SS, LB, TV, KP, SR, CC, YR, RP, MB, CA, DK, MK, SB, JM, NI, MS, IM, ON, CV, GL No competing interests declared (© 2020, Dupont et al.)
Databáze:	MEDLINE
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