Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages

Matthew J Sweet, Carol C Campbell, David P Sester, Damo Xu, Rebecca C McDonald, Katryn J Stacey, David A Hume, Foo Y Liew

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During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.
Original languageEnglish
Pages (from-to)392-9
Number of pages8
JournalJournal of Immunology
Issue number1
Publication statusPublished - 1 Jan 2002


  • Adjuvants, Immunologic
  • Animals
  • Cells, Cultured
  • Cytokines
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Drug Antagonism
  • Drug Synergism
  • Hematopoietic Stem Cells
  • Lipopolysaccharides
  • Macrophage Colony-Stimulating Factor
  • Macrophages
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Receptors, Cell Surface
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 5
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • Transcriptional Activation


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