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

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date


Document Type



Animals; Cells, 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


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.

DOI of Published Version



Cell Host Microbe. 2008 Dec 11;4(6):543-54. Link to article on publisher's site

Journal/Book/Conference Title

Cell host and microbe

Related Resources

Link to Article in PubMed

PubMed ID