You are here
Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium.
Title | Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Volkman, HE, Pozos, TC, Zheng, J, J Davis, M, Rawls, JF, Ramakrishnan, L |
Journal | Science |
Volume | 327 |
Issue | 5964 |
Pagination | 466-9 |
Date Published | 2010 Jan 22 |
ISSN | 1095-9203 |
Keywords | Animals, Antigens, Bacterial, Bacterial Proteins, Disease Models, Animal, Embryo, Nonmammalian, Enzyme Induction, Epithelial Cells, Granuloma, Macrophages, Matrix Metalloproteinase 9, Mycobacterium Infections, Nontuberculous, Mycobacterium marinum, Mycobacterium tuberculosis, Oligoribonucleotides, Antisense, Recombinant Proteins, Tuberculosis, Virulence Factors, Zebrafish, Zebrafish Proteins |
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. |
DOI | 10.1126/science.1179663 |
Alternate Journal | Science |
PubMed ID | 20007864 |
PubMed Central ID | PMC3125975 |
Grant List | F32 DK062675 / DK / NIDDK NIH HHS / United States F32 DK062675-02 / DK / NIDDK NIH HHS / United States F32 DK062675-03 / DK / NIDDK NIH HHS / United States K01 DK073695 / DK / NIDDK NIH HHS / United States K01 DK073695-01 / DK / NIDDK NIH HHS / United States K01 DK073695-02 / DK / NIDDK NIH HHS / United States K01 DK073695-03 / DK / NIDDK NIH HHS / United States K01 DK073695-04 / DK / NIDDK NIH HHS / United States R01 AI036396-19 / AI / NIAID NIH HHS / United States R01 AI054503-09 / AI / NIAID NIH HHS / United States R01 DK081426 / DK / NIDDK NIH HHS / United States R01 DK081426-01 / DK / NIDDK NIH HHS / United States R01 DK081426-02 / DK / NIDDK NIH HHS / United States |