title: TREM-1 activation modulates dsRNA induced antiviral immunity with specific enhancement of MAPK signaling and the RLRs and TLRs on macrophages.
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.
authors.affiliation: Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zj972206@163.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: gjduan@163.com.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Duan
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: 530310536@qq.com.
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: caomianfu2008@163.com.
authors.forename: Mianfu
authors.initials: M
authors.lastname: Cao
authors.affiliation: Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: youshengliu88@126.com.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation / Q000473:pathology; D007370:Interferon Type I / Q000494:pharmacology; D016086:Lentivirus / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D012330:RNA, Double-Stranded / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism*; D014162:Transfection; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D008081:Liposomes; D008562:Membrane Glycoproteins; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C
keywords: Macrophage; RLRs; TLRs; TREM-1; Up-regulation; dsRNA