TREM-1 activation modulates dsRNA induced antiviral immunity with specific enhancement of MAPK signaling and the RLRs and TLRs on macrophages

Exp Cell Res. 2016 Jul 1;345(1):70-81. doi: 10.1016/j.yexcr.2016.05.018. Epub 2016 May 26.

Abstract

Triggering receptor expressed on myeloid cells 1(TREM-1) is a newly identified member of the immunoglobulin superfamily and is extensively involved in the regulation of innate immunity. To determine the role of TREM-1 in innate antiviral immunity, we investigated TREM-1 expression and its downstream signaling effect in the murine bone marrow-derived macrophages or RAW264.7 macrophage-like mouse cell line by double-stranded RNA (dsRNA) stimulation. The level of TREM-1 expression was low at the baseline and could up-regulate markedly in dose- and time-dependent manners upon stimulation by dsRNA/poly IC. Inhibitor studies disclosed mitogen-activated protein kinase (MAPK) p38 and PI3K pathways were involved in dsRNA-induced up-regulation of TREM-1. Compared with lipopolysaccharide (LPS), the peak response of poly IC-induced TREM-1 expression is delayed, and cells pretreated with scrambled RNA presented higher expression of TREM-1 upon LPS challenge. After ligation with the agonist antibody, TREM-1 can potentiate type I interferon (IFN) production and antiviral inflammation induced by dsRNA, which is ralated to the enhanced phosphorylation of MAPKs and expression of RLRs and TLRs by TREM-1 ligation. This study is the first to show the regulatory role of TREM-1 in RLRs and TLRs expression, and these findings might enrich the understanding of the up-regulation mechanism and the function of TREM-1.

Keywords: Macrophage; RLRs; TLRs; TREM-1; Up-regulation; dsRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Bone Marrow Cells / cytology
  • Cytokines / metabolism
  • Immunity, Innate / drug effects*
  • Inflammation / pathology
  • Interferon Type I / pharmacology
  • Lentivirus / metabolism
  • Liposomes / chemistry
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Poly I-C / pharmacology
  • RAW 264.7 Cells
  • RNA, Double-Stranded / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Toll-Like Receptors / metabolism*
  • Transfection
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon Type I
  • Liposomes
  • Membrane Glycoproteins
  • RNA, Double-Stranded
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • TREM1 protein, mouse
  • Toll-Like Receptors
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Phosphatidylinositol 3-Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Poly I-C