Mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination

Helena Polena (1, 2) , Frédéric Boudou (1) , Sylvain Tilleul (1) , Nicolas Dubois-Colas (1, 2) , Cécile Lecointe (1) , Niaina Rakotosamimanana (1, 3) , Mattia Pelizzola (4) , Soa Fy Andriamandimby (3) , Vaomalala Raharimanga (5) , Patricia Charles (1) , Jean-Louis Herrmann (6, 7, 8) , Paola Ricciardi-Castagnoli (4) , Voahangy Rasolofo (9) , Brigitte Gicquel (1) , Ludovic Tailleux (1)

1 Génétique mycobactérienne - Mycobacterial genetics
2 Cellule Pasteur
3 IPM - Unité d'Epidémiologie [Antananarivo, Madagascar]
4 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
5 Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar]
6 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
7 INSERM - Institut National de la Santé et de la Recherche Médicale
8 Hôpital Raymond Poincaré [AP-HP]
9 IPM - Unité des Mycobactéries [Antananarivo, Madagascar]

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.

Domaines: Immunité innée; Maladies infectieuses

Helena Polena, Frédéric Boudou, Sylvain Tilleul, Nicolas Dubois-Colas, Cécile Lecointe, et al.. Mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination. Scientific Reports, 2016, 6 (1), pp.33162. ⟨10.1038/srep33162⟩. ⟨pasteur-03525489⟩