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.
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.
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.