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Macrophage-controlled Angiogenesis Allows Mycobacterium Tuberculosis to Disseminate

出版	2010
URL	http://books.google.com.hk/books?id=ZmOJ0AEACAAJ&hl=&source=gbs_api

註釋Tuberculosis (TB) is one of the oldest recorded human afflictions and historically is responsible for more deaths than any other single disease entity. PulmonaryTB is the most common outcome of the disease but extrapulmonary forms can occur in any organ. The aim of the present study was to decipher the mechanisms by which the airborne pathogen Mycobacterium tuberculosis leaves its primary niche to colonize and spread inside and outside the lung. A transcriptomic approach was used to investigate the host cell gene expression profile in M. tuberculosis infected human macrophages. Among the genes whose expression was significantly modulated during infection, we identified new genes encoding proteins involved in angiogenesis, including the vascular endothelial growth factor (VEGF). These angiogenic factors were readily secreted by M. tuberculosis infected macrophages and promoted the recruitment of circulating endothelial progenitor cells in order to generate new blood vessels in vivo, both in TB patients and in a murine model of the disease. Inhibiting angiogenesis through VEGF inactivation abolished mycobacterial spreading from the infection site. Here we show that M. tuberculosis exploits human macrophages to reshape the architecture of the early lesion and control its haematogenous spread to other sites. These results provide a novel conceptual framework to explain dissemination of the tubercle bacillus, and will help design novel strategies to combat this disease.