TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA
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Authors
Charrel-Dennis, MarieLatz, Eicke
Halmen, Kristen A.
Trieu-Cuot, Patrick
Fitzgerald, Katherine A.
Kasper, Dennis L.
Golenbock, Douglas T.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2008-12-10Keywords
AnimalsCells, Cultured
DNA, Bacterial
Interferon Regulatory Factor-3
Interferon Type I
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein-Serine-Threonine Kinases
Streptococcus agalactiae
Toll-Like Receptors
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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.Source
Cell Host Microbe. 2008 Dec 11;4(6):543-54. Link to article on publisher's siteDOI
10.1016/j.chom.2008.11.002Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34894PubMed ID
19064255Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.chom.2008.11.002