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

Research output: Contribution to journalArticlepeer-review

Abstract

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
Volume168
Issue number1
Publication statusPublished - 1 Jan 2002

Keywords

  • 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

Fingerprint

Dive into the research topics of 'Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages'. Together they form a unique fingerprint.

Cite this