Cutting Edge: TREM-2 Attenuates Macrophage Activation

Isaiah R. Turnbull, Susan Gilfillan, Marina Cella, Taiki Aoshi, Mark Miller, Laura Piccio, Maristela Hernandez and Marco Colonna
J Immunol September 15, 2006, 177 (6) 3520-3524; DOI: https://doi.org/10.4049/jimmunol.177.6.3520

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    TREM-2 is expressed on macrophages. A, Peritoneal macrophages were isolated before (day 1) or after (days 2–4) injection of thioglycollate. Thioglycollate-recruited macrophages express TREM-2. B, Mice were sensitized to OVA by immunization and then challenged intranasally with OVA. Macrophages recruited to the alveolar space in the sensitized mouse express TREM-2. C, The murine macrophage cell line RAW264 express TREM-2, which is down-regulated after overnight activation by IFN-γ or LPS at indicated doses. D, TREM-2 is highly expressed on BMDM from WT mice.

  • FIGURE 2.
    FIGURE 2.

    Alternative activation is sufficient but not necessary for TREM-2 expression. A, Resident peritoneal cells were isolated from WT mice and cultured for 48 h in the presence of MCSF with or without IL-4. Culture with IL-4 induced TREM-2 expression of resident peritoneal macrophages. B, Thioglycollate-recruited peritoneal cells were isolated from WT and STAT6−/− mice, and TREM-2 expression was assayed by FACS. TREM-2 is expressed independently of STAT6 expression.

  • FIGURE 3.
    FIGURE 3.

    Generation of TREM-2−/− mice. A, The TREM-2 genomic locus was deleted by homologous recombination with a construct eliminating portions of exons 3 and 4 (P represents a PST1 restriction site). B, Macrophages were derived from WT or TREM2−/− and stained with mAb 178. TREM-2 was well expressed on WT cells but absent on the TREM2−/− cells.

  • FIGURE 4.
    FIGURE 4.

    TREM-2 attenuates macrophage cytokine production. Macrophages were stimulated with the indicated concentration of LPS, zymosan, or CpG, and the levels of TNF-α and IL-6 in the supernatant were measured 24 h later. A, WT vs TREM-2−/− BMDM. TREM-2−/− cells produce increased cytokine as compared with WT cells. ∗, p < 0.05; data are representative of at least three independent experiments. B, TREM-2 accounts for the decreased cytokine response by DAP12−/− cells. WT, TREM-2, and DAP12−/− BMDM were stimulated as indicated. Both WT and DAP12−/− cells produced increased cytokine as compared with WT. There was no difference between TREM-2 and DAP12−/− cells. ∗, p < 0.05; data are representative of at least two independent experiments. C, TREM-2 inhibits the primary macrophage response to LPS. Peritoneal macrophages were isolated from WT or TREM-2−/− mice and stimulated with LPS at the indicated doses for 24 h. TREM-2−/− cells produced increased TNF-α and IL-6 in response to LPS. ∗, p < 0.05.

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