Title

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

12-10-2008

Document Type

Article

Subjects

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

Disciplines

Immunology and Infectious Disease

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.

Rights and Permissions

Citation: 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

19064255