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

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 investiga...

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Detalles Bibliográficos
Autores principales: Polena, Helena, Boudou, Frédéric, Tilleul, Sylvain, Dubois-Colas, Nicolas, Lecointe, Cécile, Rakotosamimanana, Niaina, Pelizzola, Mattia, Andriamandimby, Soa Fy, Raharimanga, Vaomalala, Charles, Patricia, Herrmann, Jean-Louis, Ricciardi-Castagnoli, Paola, Rasolofo, Voahangy, Gicquel, Brigitte, Tailleux, Ludovic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018821/
https://www.ncbi.nlm.nih.gov/pubmed/27616470
http://dx.doi.org/10.1038/srep33162
Descripción
Sumario: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.