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TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.
Charrel-Dennis M., Latz E., A. Halmen K., Trieu-Cuot P., A. Fitzgerald K., L. Kasper D., T. Golenbock D.
Cell Host & Microbe 4, 6 (2008) 543-54 - http://hal.archives-ouvertes.fr/hal-00346660
Sciences du Vivant/Microbiologie et Parasitologie
(19064255)
TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.
Marie Charrel-Dennis1, Eicke Latz1, Kristen A. Halmen1, Patrick Trieu-Cuot2, Katherine A. Fitzgerald1, Dennis L. Kasper3, 4, Douglas T. Golenbock1
1 :  Division of Infectious Diseases and Immunology
University of Massachusetts Medical School
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605
États-Unis
2 :  Biologie des Bactéries Pathogènes à Gram-positif
Institut Pasteur de Paris – CNRS : URA2172
25-28 rue du Docteur Roux F-75724 Paris Cedex 15
France
3 :  Channing Laboratory
Brigham and Women's Hospital - Harvard Medical School
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
États-Unis
4 :  Department of Microbiology and Molecular Genetics
Harvard Medical School
Harvard Medical School, Boston, MA 02115
États-Unis
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.
Anglais

Articles dans des revues avec comité de lecture
10.1016/j.chom.2008.11.002
Cell Host & Microbe
Publisher Cell Press
internationale
11/12/2008
4
6
543-54