Tuberculosis Exacerbates HIV-1 Infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages.

Autor: Souriant S; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina., Balboa L; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina; Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina., Dupont M; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina., Pingris K; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Kviatcovsky D; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina; Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina., Cougoule C; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina., Lastrucci C; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; Centre for Genomic Regulation, Barcelona, Spain., Bah A; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Gasser R; Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France., Poincloux R; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Raynaud-Messina B; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Al Saati T; INSERM/UPS/ENVT-US006/CREFRE, Service d'Histopathologie, CHU Purpan, 31024 Toulouse, France., Inwentarz S; Instituto de Tisioneumonologia 'Raúl F. Vaccarezza,' Universitad de Buenos Aires, Argentina., Poggi S; Instituto de Tisioneumonologia 'Raúl F. Vaccarezza,' Universitad de Buenos Aires, Argentina., Moraña EJ; Instituto de Tisioneumonologia 'Raúl F. Vaccarezza,' Universitad de Buenos Aires, Argentina., González-Montaner P; Instituto de Tisioneumonologia 'Raúl F. Vaccarezza,' Universitad de Buenos Aires, Argentina., Corti M; Division de SIDA, Hospital de Infecciosas Dr. F.J. Muñiz, Buenos Aires, Argentina., Lagane B; Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France., Vergne I; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France., Allers C; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA., Kaushal D; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA., Kuroda MJ; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA., Sasiain MDC; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina; Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina., Neyrolles O; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and 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' (1167), Toulouse, France, and Buenos Aires, Argentina., 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' (1167), Toulouse, France, and Buenos Aires, Argentina. Electronic address: lugo@ipbs.fr., Vérollet C; Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; International Associated Laboratory (LIA) CNRS 'IM-TB/HIV' (1167), Toulouse, France, and Buenos Aires, Argentina. Electronic address: verollet@ipbs.fr.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2019 Mar 26; Vol. 26 (13), pp. 3586-3599.e7.
DOI: 10.1016/j.celrep.2019.02.091
Abstrakt: The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironment, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity. Furthermore, HIV-1/Mtb co-infected patients display an accumulation of M(IL-10) macrophage markers (soluble CD163 and MerTK). These M(IL-10) macrophages form direct cell-to-cell bridges, which we identified as tunneling nanotubes (TNTs) involved in viral transfer. TNT formation requires the IL-10/STAT3 signaling pathway, and targeted inhibition of TNTs substantially reduces the enhancement of HIV-1 cell-to-cell transfer and overproduction in M(IL-10) macrophages. Our study reveals that TNTs facilitate viral transfer and amplification, thereby promoting TNT formation as a mechanism to be explored in TB/AIDS potential therapeutics.
(Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE