PUBLICATION
The role of the granuloma in expansion and dissemination of early tuberculous infection
- Authors
- Davis, J.M., and Ramakrishnan, L.
- ID
- ZDB-PUB-090116-15
- Date
- 2009
- Source
- Cell 136(1): 37-49 (Journal)
- Registered Authors
- Davis, James M., Ramakrishnan, Lalita
- Keywords
- HUMDISEASE, CELLIMMUNO, MICROBIO
- MeSH Terms
-
- Animals
- Apoptosis
- Chemotaxis
- Granuloma/immunology*
- Granuloma/microbiology*
- Granuloma/pathology
- Host-Pathogen Interactions*
- Humans
- Macrophages/cytology
- Macrophages/immunology
- Macrophages/microbiology
- Mycobacterium Infections/immunology
- Mycobacterium Infections/pathology
- Mycobacterium Infections, Nontuberculous/immunology*
- Mycobacterium Infections, Nontuberculous/pathology
- Mycobacterium marinum/immunology
- Mycobacterium tuberculosis
- Phagocytosis
- Tuberculosis/immunology*
- Tuberculosis/pathology
- Virulence Factors
- Zebrafish
- PubMed
- 19135887 Full text @ Cell
Citation
Davis, J.M., and Ramakrishnan, L. (2009) The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell. 136(1):37-49.
Abstract
Granulomas, organized aggregates of immune cells, form in response to persistent stimuli and are hallmarks of tuberculosis. Tuberculous granulomas have long been considered host-protective structures formed to contain infection. However, work in zebrafish infected with Mycobacterium marinum suggests that granulomas contribute to early bacterial growth. Here we use quantitative intravital microscopy to reveal distinct steps of granuloma formation and assess their consequence for infection. Intracellular mycobacteria use the ESX-1/RD1 virulence locus to induce recruitment of new macrophages to, and their rapid movement within, nascent granulomas. This motility enables multiple arriving macrophages to efficiently find and phagocytose infected macrophages undergoing apoptosis, leading to rapid, iterative expansion of infected macrophages and thereby bacterial numbers. The primary granuloma then seeds secondary granulomas via egress of infected macrophages. Our direct observations provide insight into how pathogenic mycobacteria exploit the granuloma during the innate immune phase for local expansion and systemic dissemination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping