PUBLICATION
Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant
- Authors
- Volkman, H.E., Clay, H., Beery, D., Chang, J.C., Sherman, D.R., and Ramakrishnan, L.
- ID
- ZDB-PUB-041029-11
- Date
- 2004
- Source
- PLoS Biology 2(11): e367 (Journal)
- Registered Authors
- Chang, Jenny, Clay, Hilary, Ramakrishnan, Lalita, Volkman, Hannah
- Keywords
- Macrophages, Embryos, Granulomas, Mycobacterium tuberculosis, Fluorescence imaging, Zebrafish, Bacterial diseases, Virulence factors
- MeSH Terms
-
- Animals
- Cell Death
- Cell Line
- Cells, Cultured
- Chemotaxis
- Granuloma/microbiology
- In Situ Nick-End Labeling
- Macrophage Activation
- Macrophages/metabolism
- Macrophages/microbiology
- Mice
- Microscopy, Video
- Mutation
- Mycobacterium Infections/microbiology*
- Mycobacterium Infections/pathology
- Mycobacterium tuberculosis/pathogenicity*
- Ranidae/microbiology*
- Time Factors
- Tuberculoma/microbiology*
- Tuberculosis/microbiology*
- Virulence
- Zebrafish
- PubMed
- 15510227 Full text @ PLoS Biol.
Citation
Volkman, H.E., Clay, H., Beery, D., Chang, J.C., Sherman, D.R., and Ramakrishnan, L. (2004) Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant. PLoS Biology. 2(11):e367.
Abstract
Granulomas are organized host immune structures composed of tightly interposed macrophages and other cells that form in response to a variety of persistent stimuli, both infectious and noninfectious. The tuberculous granuloma is essential for host containment of mycobacterial infection, although it does not always eradicate it. Therefore, it is considered a host-beneficial, if incompletely efficacious, immune response. The Mycobacterium RD1 locus encodes a specialized secretion system that promotes mycobacterial virulence by an unknown mechanism. Using transparent zebrafish embryos to monitor the infection process in real time, we found that RD1-deficient bacteria fail to elicit efficient granuloma formation despite their ability to grow inside of infected macrophages. We showed that macrophages infected with virulent mycobacteria produce an RD1-dependent signal that directs macrophages to aggregate into granulomas. This Mycobacterium-induced macrophage aggregation in turn is tightly linked to intercellular bacterial dissemination and increased bacterial numbers. Thus, mycobacteria co-opt host granulomas for their virulence.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping