TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.

Marie Charrel-Dennis (1) , Eicke Latz (1) , Kristen A. Halmen (1) , Patrick Trieu-Cuot (2) , Katherine A. Fitzgerald (1) , Dennis L. Kasper (3, 4) , Douglas T. Golenbock (1)

1 Division of Infectious Diseases and Immunology
2 Biologie des Bactéries Pathogènes à Gram-positif
3 Channing Laboratory
4 Department of Microbiology and Molecular Genetics

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.

Domaines: Microbiologie et Parasitologie

Marie Charrel-Dennis, Eicke Latz, Kristen A. Halmen, Patrick Trieu-Cuot, Katherine A. Fitzgerald, et al.. TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.. Cell Host and Microbe, 2008, 4 (6), pp.543-54. ⟨10.1016/j.chom.2008.11.002⟩. ⟨hal-00346660⟩