Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination

Sandra Ebert, Joachim Gerber, Steffi Bader, Frank Mühlhauser, Katrin Brechtel, Timothy J Mitchell, Roland Nau

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)


Microglial cells express Toll-like receptors (TLRs) recognising exogenous and endogenous ligands. Upon stimulation with agonists of TLR2, TLR4, and TLR9, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were released by primary mouse microglial cell cultures. Endotoxin was most potent in stimulating microglia followed by pneumolysin, cytosine-guanosine (CpG) oligodesoxynucleotide (ODN), and Tripalmitoyl-S-glyceryl-cysteine. Maximum stimulation of TLR2, TLR4, and TLR9 resulted in approximately equal amounts of nitric oxide release. Pneumolysin was a potent activator of microglial cells; at high concentrations, it reduced cell viability. No cytotoxicity was noted with the other TLR agonists. Costimulation with maximum concentrations of two TLR agonists did not further increase nitric oxide release. Costimulation with submaximum concentrations was additive or supraadditive, suggesting that even low concentrations of products of infectious agents can lead to microglial activation via TLRs.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalJournal of Neuroimmunology
Issue number1-2
Publication statusPublished - Feb 2005


  • Acholeplasma laidlawii
  • Adjuvants, Immunologic
  • Animals
  • Bacterial Proteins
  • Cells, Cultured
  • CpG Islands
  • Cysteine
  • DNA-Binding Proteins
  • Dose-Response Relationship, Immunologic
  • Drug Combinations
  • Lipopolysaccharides
  • Lipoproteins
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • Nitric Oxide
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Streptolysins
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9


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