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TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.
- Source :
-
Cell host & microbe [Cell Host Microbe] 2008 Dec 11; Vol. 4 (6), pp. 543-54. - Publication Year :
- 2008
-
Abstract
- Type I interferon (IFN) is an important host defense cytokine against intracellular pathogens, mainly viruses. In assessing IFN production in response to group B streptococcus (GBS), we find that IFN-beta was produced by macrophages upon stimulation with both heat-killed and live GBS. Exposure of macrophages to heat-killed GBS activated a Toll-like receptor (TLR)-dependent pathway, whereas live GBS activated a TLR/NOD/RIG-like receptor (RLR)-independent pathway. This latter pathway required bacterial phagocytosis, proteolytic bacterial degradation, and phagolysosomal membrane destruction by GBS pore-forming toxins, leading to the release of bacterial DNA into the cytosol. GBS DNA in the cytosol induced IFN-beta production via a pathway dependent on the activation of the serine-threonine kinase TBK1 and phosphorylation of the transcription factor IRF3. Thus, activation of IFN-alpha/-beta production during infection with GBS, commonly considered an extracellular pathogen, appears to result from the interaction of GBS DNA with a putative intracellular DNA sensor or receptor.
- Subjects :
- Animals
Cells, Cultured
Interferon Regulatory Factor-3 metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Serine-Threonine Kinases metabolism
DNA, Bacterial immunology
Interferon Type I immunology
Macrophages immunology
Macrophages microbiology
Streptococcus agalactiae immunology
Toll-Like Receptors immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1934-6069
- Volume :
- 4
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell host & microbe
- Publication Type :
- Academic Journal
- Accession number :
- 19064255
- Full Text :
- https://doi.org/10.1016/j.chom.2008.11.002