Disparate expression of IL-12 by SJL/J and B10.S macrophages during Theiler's virus infection is associated with activity of TLR7 and mitogen-activated protein kinases

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Differences in components of innate anti-viral immune responses may account for the contrast in susceptibility to Theiler's murine encephalomyelitis virus (TMEV) between SJL/J and B10.S mice. Herein, the expression of IL-12, interferon (IFN)-β, Toll-like receptors 3 (TLR3), TLR7, and mitogen-activated protein (MAP)-kinases was evaluated in SJL/J and B10.S macrophages infected with TMEV. Twenty-four hours after infection, SJL/J macrophages exhibited higher levels of TMEV RNA, IL-12 p40, and TLR3 but lower levels of IL-12 p70 and the IL-12 p35 subunit compared with B10.S macrophages. Addition of exogenous IL-12 p70 or IFN-β increased the resistance of SJL/J macrophages to TMEV infection. To assess MAP-kinases, macrophages were pretreated with the p38 MAP-kinase inhibitor SB203580 or extracellular signal-regulated kinases (ERK) MAP-kinase inhibitor U0126 before TMEV infection. U0126 reduced SJL/J but increased B10.S macrophage expression of IL-12 p40 and p70 in response to TMEV. U0126 decreased the IL-12 p35 response of SJL/J macrophages. To assess TLR7, SJL/J and B10.S macrophages were stimulated with loxoribine, a TLR7 ligand. Loxoribine induced more IL-12 p70 production and p35 expression in B10.S than SJL/J macrophages. U0126 increased loxoribine-induced expression of IL-12 p40 and IL-12 p70 in B10.S but not SJL/J macrophages. Thus, differences in production of IL-12 p70 due to expression of the p35 subunit and in activity of TLR7, as well as activation of factors downstream of ERK MAP-kinases likely underlie the disparity in innate immunity between SJL/J and B10.S macrophages to TMEV.

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalMicrobes and Infection
Volume7
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • ERK1/2
  • IL-12
  • MAP-kinases
  • TMEV
  • Toll-like receptors
  • p38

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Disparate expression of IL-12 by SJL/J and B10.S macrophages during Theiler's virus infection is associated with activity of TLR7 and mitogen-activated protein kinases'. Together they form a unique fingerprint.

  • Cite this