PUBLICATION
Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death
- Authors
- Clay, H., Volkman, H.E., and Ramakrishnan, L.
- ID
- ZDB-PUB-080826-4
- Date
- 2008
- Source
- Immunity 29(2): 283-294 (Journal)
- Registered Authors
- Clay, Hilary, Ramakrishnan, Lalita, Volkman, Hannah
- Keywords
- CELLIMMUNO
- MeSH Terms
-
- Animals
- Apoptosis
- Cell Death
- Cell Movement
- Cytokines/immunology
- Cytokines/metabolism
- Embryo, Nonmammalian
- Granuloma/immunology*
- Granuloma/metabolism
- Granuloma/microbiology
- Immunity, Innate
- Macrophages/immunology*
- Macrophages/microbiology*
- Mycobacterium Infections, Nontuberculous/immunology*
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium marinum/growth & development
- Mycobacterium marinum/immunology*
- Mycobacterium marinum/physiology
- Receptors, Tumor Necrosis Factor, Type I/immunology
- Receptors, Tumor Necrosis Factor, Type I/metabolism*
- Signal Transduction*
- Tumor Necrosis Factors/immunology
- Tumor Necrosis Factors/metabolism*
- Zebrafish/immunology
- Zebrafish/microbiology
- PubMed
- 18691913 Full text @ Immunity
Citation
Clay, H., Volkman, H.E., and Ramakrishnan, L. (2008) Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity. 29(2):283-294.
Abstract
Tumor necrosis factor (TNF), a key effector in controlling tuberculosis, is thought to exert protection by directing formation of granulomas, organized aggregates of macrophages and other immune cells. Loss of TNF signaling causes progression of tuberculosis in humans, and the increased mortality of Mycobacterium tuberculosis-infected mice is associated with disorganized necrotic granulomas, although the precise roles of TNF signaling preceding this endpoint remain undefined. We monitored transparent Mycobacterium marinum-infected zebrafish live to conduct a stepwise dissection of how TNF signaling operates in mycobacterial pathogenesis. We found that loss of TNF signaling caused increased mortality even when only innate immunity was operant. In the absence of TNF, intracellular bacterial growth and granuloma formation were accelerated and was followed by necrotic death of overladen macrophages and granuloma breakdown. Thus, TNF is not required for tuberculous granuloma formation, but maintains granuloma integrity indirectly by restricting mycobacterial growth within macrophages and preventing their necrosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping