CpG DNA activates survival in murine macrophages through TLR9 and the phosphatidylinositol 3-kinase-Akt pathway

David P Sester, Kristian Brion, Angela Trieu, Helen S Goodridge, Tara L Roberts, Jasmyn Dunn, David A Hume, Katryn J Stacey, Matthew J Sweet

Research output: Contribution to journalArticlepeer-review

Abstract

Bacterial CpG-containing (CpG) DNA promotes survival of murine macrophages and triggers production of proinflammatory mediators. The CpG DNA-induced inflammatory response is mediated via TLR9, whereas a recent study reported that activation of the Akt prosurvival pathway occurs via DNA-dependent protein kinase (DNA-PK) and independently of TLR9. We show, in this study, that Akt activation and survival of murine bone marrow-derived macrophages (BMM) triggered by CpG-containing phosphodiester oligodeoxynucleotides or CpG-containing phosphorothioate oligodeoxynucleotides was completely dependent on TLR9. In addition, survival triggered by CpG-containing phosphodiester oligodeoxynucleotides was not compromised in BMM from SCID mice that express a catalytically inactive form of DNA-PK. CpG DNA-induced survival of BMM was inhibited by the PI3K inhibitor, LY294002, but not by the MEK1/2 inhibitor, PD98059. The effect of LY294002 was specific to survival, because treatment of BMM with LY294002 affected CpG DNA-induced TNF-alpha production only modestly. Therefore, CpG DNA activates macrophage survival via TLR9 and the PI3K-Akt pathway and independently of DNA-PK and MEK-ERK.
Original languageEnglish
Pages (from-to)4473-80
Number of pages8
JournalJournal of Immunology
Volume177
Issue number7
Publication statusPublished - 1 Oct 2006

Keywords

  • Animals
  • Bone Marrow Cells
  • Cell Survival
  • Cells, Cultured
  • Chromones
  • CpG Islands
  • DNA
  • Enzyme Inhibitors
  • Flow Cytometry
  • Immunoblotting
  • Macrophage Activation
  • Macrophages
  • Mice
  • Morpholines
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha

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