CpG-Induced IFNγ expands TLR4-specific IL-18 responses in vivo

Sameer Gupta, Meetha P. Gould, Jennifer DeVecchio, David H. Canaday, Jeffery J. Auletta, Frederick P. Heinzel

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Serum IL-18 responses to LPS increase after pretreatment with CpG-containing DNA. Compared to saline-pretreated controls, mice pretreated with CpG for two days produced 20-fold more serum IL-18 when challenged with lipopolysaccharide (LPS). In contrast, IFNγ-deficiency or anti-IFNγ pretreatment reduced CpG-expanded IL-18 responses to LPS by 67 and 83%, respectively. Mice pretreated with either IFNγ or CpG comparably increased LPS-inducible serum IL-18 responses. LPS, compared to challenge with other TLR agonists, was best able to trigger high serum IL-18 levels in CpG-pretreated mice and this response was TLR4-dependent. CpG, compared to pretreatment with other TLR agonists, optimally expanded LPS-induced IL-18 responses that correlated with higher levels of circulating IFNγ levels prior to LPS challenge. High-level serum IL-18 responses were caspase-1-dependent and P2X7 receptor-independent. We conclude that CpG promotes high-level IL-18 synthesis by an IFNγ-dependent and IFNγ-sufficient mechanism in vivo that is optimally triggered by LPS.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalCellular Immunology
Volume243
Issue number2
DOIs
StatePublished - Oct 2006
Externally publishedYes

Bibliographical note

Funding Information:
Fred Heinzel is supported by the VA Medical Research Service and by NIH Grant AI45602, Jeff Auletta by AI57801 and Sameer Gupta by T32 HL07889. We thank Drs. Eric Pearlman, George Dubyak and Michelle Lin for discussion, encouragement and sharing of reagents in these studies.

Keywords

  • Interferon, type II
  • Interleukin-18
  • Mice
  • Purinergic P2
  • Receptors
  • Toll-like receptor 9

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