Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Volkman, HE; Pozos, TC; Zheng, J; Davis, JM; Rawls, JF; Ramakrishnan, L
Published Date
- January 22, 2010
Published In
Volume / Issue
- 327 / 5964
Start / End Page
- 466 - 469
PubMed ID
- 20007864
Pubmed Central ID
- PMC3125975
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.1179663
Language
- eng
Conference Location
- United States