Contributors: Génétique mycobactérienne - Mycobacterial genetics; Institut Pasteur [Paris] (IP); Cellule Pasteur; Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité; Unité d'Epidémiologie [Antananarivo, Madagascar] (IPM); Institut Pasteur de Madagascar; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP); Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB); Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar]; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ); Institut National de la Santé et de la Recherche Médicale (INSERM); Hôpital Raymond Poincaré [AP-HP]; Unité des Mycobactéries [Antananarivo, Madagascar] (IPM); This research project was co-financed by Institut Pasteur and the European Commission, as part of the 6th Framework Programme, contract numbers LSH-2003-2.3.0-1 and LSHP-CT-2003-503367, the 7th Framework Programme, grant number HEALTH-F3-2009-241745.; European Project: 241745,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,NEWTBVAC(2010); Tailleux, Ludovic; Discovery and preclinical development of new generation tuberculosis vaccines - NEWTBVAC - - EC:FP7:HEALTH2010-01-01 - 2014-02-28 - 241745 - VALID
نبذة مختصرة : The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly understood. Herein, we used a transcriptomic approach to investigate the host cell gene expression profile in M. tuberculosis–infected human macrophages (ΜΦ). We identified 33 genes, encoding proteins involved in angiogenesis, for which the expression was significantly modified during infection, and we show that the potent angiogenic factor VEGF is secreted by M. tuberculosis-infected ΜΦ, in an RD1-dependent manner. In vivo these factors promote the formation of blood vessels in murine models of the disease. Inhibiting angiogenesis, via VEGF inactivation, abolished mycobacterial spread from the infection site. In accordance with our in vitro and in vivo results, we show that the level of VEGF in TB patients is elevated and that endothelial progenitor cells are mobilized from the bone marrow. These results strongly strengthen the most recent data suggesting that mycobacteria take advantage of the formation of new blood vessels to disseminate.
Processing Request
No Comments.