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

eLife

Thien-Phong Vu Manh¹  Renaud Poincloux²  Yoann Rombouts²  Myriam Ben Neji²  Karine Pingris²  Stella Rousset²  Olivier Neyrolles³  Geanncarlo Lugo-Villarino³  Isabelle Maridonneau-Parini³  Christel Vérollet³  Maeva Dupont³  Shanti Souriant³  Céline Cougoule³  Maria del Carmen Sasiain⁴  Luciana Balboa⁴  Nuria Izquierdo-Useros⁵  Susana Benet⁶  Javier Martinez-Picado⁷  Carolina Allers⁸  Marcelo J Kuroda⁸  Deepak Kaushal⁸ 

[1] Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France;Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France;Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France;International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France;International associated laboratory (LIA) CNRS 'IM-TB/HIV', Toulouse, France;Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina;IrsiCaixa AIDS Research Institute, Department of Retrovirology, Badalona, Spain;Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain;IrsiCaixa AIDS Research Institute, Department of Retrovirology, Badalona, Spain;Universitat Autònoma de Barcelona, Barcelona, Spain;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;Tulane National Primate Research Center, Department of Microbiology and Immunology, School of Medicine, Tulane University, Covington, United States;

关键词: macrophages;    HIV;    mycobacterium tuberculosis;    tunneling natotubes;    interferons;    co-infection;    Human;    Rhesus macaque;   

DOI  :  10.7554/eLife.52535

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY