1. TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.
- Author
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Charrel-Dennis M, Latz E, Halmen KA, Trieu-Cuot P, Fitzgerald KA, Kasper DL, and Golenbock DT
- 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
- 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.
- Published
- 2008
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