|ZFIN ID: ZDB-PUB-041029-11|
Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant
Volkman, H.E., Clay, H., Beery, D., Chang, J.C., Sherman, D.R., and Ramakrishnan, L.
|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|
|PubMed:||15510227 Full text @ PLoS Biol.|
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.
ABSTRACTGranulomas 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.
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