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

• TREM-1 on the macrophages is raised in dose- and time-dependent manners by dsRNA.
• TREM-1 ligation can enhance the antivirus inflammation and IFN-β induced by dsRNA.
• TREM-1 activation can enhance MAPKs phosphorylation and expression of RLRs and TLRs.

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.