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Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant

by Volkman, Hannah E , Clay, Hilary , Ramakrishnan, Lalita , Beery, Dana , Chang, Jennifer C. W , Sherman, David R

in Animals / Bacteria / Cell Death / Cell Line / Cells, Cultured / Chemotaxis / Danio (Zebrafish) / Experiments / Gene expression / Granuloma - microbiology / Immune response / Immunology / In Situ Nick-End Labeling / Infections / Infectious Diseases / Macrophage Activation / Macrophages - metabolism / Macrophages - microbiology / Mice / Microbiology / Microscopy, Video / Mutation / Mycobacterium Infections - microbiology / Mycobacterium Infections - pathology / Mycobacterium tuberculosis - pathogenicity / Ranidae - microbiology / Time Factors / Tuberculoma - microbiology / Tuberculosis - microbiology / Virulence / Zebrafish

2004

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Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant

by Volkman, Hannah E , Clay, Hilary , Ramakrishnan, Lalita , Beery, Dana , Chang, Jennifer C. W , Sherman, David R

2004

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Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant

by Volkman, Hannah E , Clay, Hilary , Ramakrishnan, Lalita , Beery, Dana , Chang, Jennifer C. W , Sherman, David R

2004

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Journal Article

Tuberculous Granuloma Formation Is Enhanced by a Mycobacterium Virulence Determinant

Volkman, Hannah E,

Clay, Hilary,

Ramakrishnan, Lalita,

Beery, Dana,

Chang, Jennifer C. W,

Sherman, David R

2004

Overview

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.

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Public Library of Science,Public Library of Science (PLoS)

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