PUBLICATION
Tuberculous Granuloma Induction via Interaction of a Bacterial Secreted Protein with Host Epithelium
- Authors
- Volkman, H.E., Pozos, T.C., Zheng, J., Davis, J.M., Rawls, J.F., and Ramakrishnan, L.
- ID
- ZDB-PUB-091221-10
- Date
- 2010
- Source
- Science (New York, N.Y.) 327(5964): 466-469 (Journal)
- Registered Authors
- Davis, James M., Pozos, Tamara Christine, Ramakrishnan, Lalita, Rawls, John F., Volkman, Hannah, Zheng, John
- Keywords
- none
- Datasets
- GEO:GSE8846, GEO:GSE8327
- MeSH Terms
-
- Antigens, Bacterial/genetics
- Antigens, Bacterial/metabolism*
- Disease Models, Animal
- Granuloma/metabolism
- Granuloma/microbiology*
- Oligoribonucleotides, Antisense
- Embryo, Nonmammalian/microbiology
- Zebrafish/embryology
- Matrix Metalloproteinase 9/genetics
- Matrix Metalloproteinase 9/metabolism*
- Enzyme Induction
- Tuberculosis/microbiology*
- Mycobacterium marinum/growth & development
- Mycobacterium marinum/metabolism
- Mycobacterium marinum/pathogenicity*
- Epithelial Cells/enzymology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology*
- Recombinant Proteins/metabolism
- Animals
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism*
- Mycobacterium tuberculosis/genetics
- Mycobacterium tuberculosis/pathogenicity
- Virulence Factors/genetics
- Virulence Factors/metabolism*
- Macrophages/microbiology
- Macrophages/physiology
- PubMed
- 20007864 Full text @ Science
Citation
Volkman, H.E., Pozos, T.C., Zheng, J., Davis, J.M., Rawls, J.F., and Ramakrishnan, L. (2010) Tuberculous Granuloma Induction via Interaction of a Bacterial Secreted Protein with Host Epithelium. Science (New York, N.Y.). 327(5964):466-469.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping