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Tuberculous granuloma formation is enhanced by a mycobacterium virulence determinant.
Title | Tuberculous granuloma formation is enhanced by a mycobacterium virulence determinant. |
Publication Type | Journal Article |
Year of Publication | 2004 |
Authors | Volkman, HE, Clay, H, Beery, D, Chang, JCW, Sherman, DR, Ramakrishnan, L |
Journal | PLoS Biol |
Volume | 2 |
Issue | 11 |
Pagination | e367 |
Date Published | 2004 Nov |
ISSN | 1545-7885 |
Keywords | Animals, Cell Death, Cell Line, Cells, Cultured, Chemotaxis, Granuloma, In Situ Nick-End Labeling, Macrophage Activation, Macrophages, Mice, Microscopy, Video, Mutation, Mycobacterium Infections, Mycobacterium tuberculosis, Ranidae, Time Factors, Tuberculoma, Tuberculosis, Virulence, Zebrafish |
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. |
DOI | 10.1371/journal.pbio.0020367 |
Alternate Journal | PLoS Biol. |
PubMed ID | 15510227 |
PubMed Central ID | PMC524251 |
Grant List | AI054503 / AI / NIAID NIH HHS / United States HL64550 / HL / NHLBI NIH HHS / United States HL68533 / HL / NHLBI NIH HHS / United States R01 AI36396 / AI / NIAID NIH HHS / United States T32 GM07270 / GM / NIGMS NIH HHS / United States |