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

M Charrel-Dennis, E Latz, KA Halmen, P Trieu-Cuot… - Cell host & …, 2008 - cell.com
M Charrel-Dennis, E Latz, KA Halmen, P Trieu-Cuot, KA Fitzgerald, DL Kasper
Cell host & microbe, 2008cell.com
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-β 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 …
Summary
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-β 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-β 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-α/-β 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.
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