Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes

Bouchon, Axel; Dietrich, Jes; Colonna, Marco

doi:10.4049/jimmunol.164.10.4991

Cited by 1,056 publications

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“…Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently identified cell surface molecule that is found on neutrophils and monocytes (7)(8)(9). TREM-1 is a member of the 30-kd immunoglobulin superfamily, and its expression is up-regulated by lipoteichoic acid or lipopolysaccharide (LPS) (7,8,10,11).…”

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“…TREM-1 is a member of the 30-kd immunoglobulin superfamily, and its expression is up-regulated by lipoteichoic acid or lipopolysaccharide (LPS) (7,8,10,11). TREM-1 activates monocytes through the transmembrane adaptor protein DAP12 (7)(8)(9). Targeting of TREM-1 expressed by neutrophils and monocytes with agonist monoclonal antibodies promotes the production of various inflammatory cytokines, such as IL-8, MCP-1, tumor necrosis factor ␣ (TNF␣), granulocytemacrophage colony-stimulating factor, and IL-1␤ (8,10,11).…”

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“…TREM-1 activates monocytes through the transmembrane adaptor protein DAP12 (7)(8)(9). Targeting of TREM-1 expressed by neutrophils and monocytes with agonist monoclonal antibodies promotes the production of various inflammatory cytokines, such as IL-8, MCP-1, tumor necrosis factor ␣ (TNF␣), granulocytemacrophage colony-stimulating factor, and IL-1␤ (8,10,11). In addition, marked enhancement of TNF␣, IL-1␤, and MCP-1 production by monocytes incubated with agonist monoclonal antibodies occurs when LPS is added as a costimulant, indicating that TREM-1 can amplify inflammatory responses initiated by Toll-like receptors (TLRs) (8,10,11).…”

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confidence: 99%

“…Targeting of TREM-1 expressed by neutrophils and monocytes with agonist monoclonal antibodies promotes the production of various inflammatory cytokines, such as IL-8, MCP-1, tumor necrosis factor ␣ (TNF␣), granulocytemacrophage colony-stimulating factor, and IL-1␤ (8,10,11). In addition, marked enhancement of TNF␣, IL-1␤, and MCP-1 production by monocytes incubated with agonist monoclonal antibodies occurs when LPS is added as a costimulant, indicating that TREM-1 can amplify inflammatory responses initiated by Toll-like receptors (TLRs) (8,10,11). Although natural ligands for TREM-1 remain to be identified, its pathophysiologic significance in acute inflammation has already been demonstrated in murine models of septic shock, in which competition for binding to TREM-1 by a recombinant TREM-1 fusion protein or synthetic soluble TREM-1 (sTREM-1) was shown to protect mice against lethal LPS challenge or bacterial sepsis (11,12).…”

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Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

Murakami

Akahoshi²,

Hayashi

et al. 2006

Arthritis & Rheumatism

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Objective. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM-1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM-1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM-1 expression by MSU crystal-stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation was determined. The biologic role of TREM-1 in crystal-induced cytokine production by resident peritoneal macrophages was also investigated.Methods. TREM-1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model was determined by quantitative real-time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti-TREM-1 agonist antibody was determined by enzymelinked immunosorbent assay.Results. TREM-1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM-1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti-TREM-1 agonist antibody synergistically increased the production of both interleukin-1␤ and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM-1 expression in infiltrating leukocytes in a murine air-pouch model of crystalinduced acute inflammation.Conclusion. These findings suggest that rapid induction of TREM-1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses.

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Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

Murakami

Akahoshi²,

Hayashi

et al. 2006

Arthritis & Rheumatism

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Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement

Guerreiro

Lohmann²,

Brás³

et al. 2012

JAMA Neurol

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To identify new genes and risk factors associated with frontotemporal dementia (FTD). Several genes and loci have been associated with different forms of FTD, but a large number of families with dementia do not harbor mutations in these genes.Design: Whole-exome sequencing and whole-genome genotyping were performed in all patients. Genetic variants obtained from whole-exome sequencing were integrated with the data obtained from whole-genome genotyping.

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Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement

Guerreiro¹,

Lohmann²,

Brás³

et al. 2013

JAMA Neurol

308

229

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Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes

Cited by 1,056 publications

References 12 publications

Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement

Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement

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