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Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium.


ABSTRACT: Granulomas, organized aggregates of immune cells, are a hallmark of tuberculosis and have traditionally been thought to restrict mycobacterial growth. However, analysis of Mycobacterium marinum in zebrafish has shown that the early granuloma facilitates mycobacterial growth; uninfected macrophages are recruited to the granuloma where they are productively infected by M. marinum. Here, we identified the molecular mechanism by which mycobacteria induce granulomas: The bacterial secreted protein 6-kD early secreted antigenic target (ESAT-6), which has long been implicated in virulence, induced matrix metalloproteinase-9 (MMP9) in epithelial cells neighboring infected macrophages. MMP9 enhanced recruitment of macrophages, which contributed to nascent granuloma maturation and bacterial growth. Disruption of MMP9 function attenuated granuloma formation and bacterial growth. Thus, interception of epithelial MMP9 production could hold promise as a host-targeting tuberculosis therapy.

SUBMITTER: Volkman HE 

PROVIDER: S-EPMC3125975 | biostudies-other | 2010 Jan

REPOSITORIES: biostudies-other

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Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium.

Volkman Hannah E HE   Pozos Tamara C TC   Zheng John J   Davis J Muse JM   Rawls John F JF   Ramakrishnan Lalita L  

Science (New York, N.Y.) 20091210 5964


Granulomas, organized aggregates of immune cells, are a hallmark of tuberculosis and have traditionally been thought to restrict mycobacterial growth. However, analysis of Mycobacterium marinum in zebrafish has shown that the early granuloma facilitates mycobacterial growth; uninfected macrophages are recruited to the granuloma where they are productively infected by M. marinum. Here, we identified the molecular mechanism by which mycobacteria induce granulomas: The bacterial secreted protein 6-  ...[more]

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