Cutting edge: TREM-2 attenuates macrophage activation.
The triggering receptor expressed on myeloid cells 2 (TREM-2) delivers intracellular signals through the adaptor DAP12 to regulate myeloid cell function both within and outside the immune system. The role of TREM-2 in immunity has been obscured by the failure to detect expression of the TREM-2 protein in vivo. In this study, we show that TREM-2 is expressed on macrophages infiltrating the tissues from the circulation and that alternative activation with IL-4 can induce TREM-2. TREM-2 expression is abrogated by macrophage maturation with LPS of IFN-gamma. Using TREM-2(-/-) mice, we find that TREM-2 functions to inhibit cytokine production by macrophages in response to the TLR ligands LPS, zymosan, and CpG. Furthermore, we find that TREM-2 completely accounts for the increased cytokine production previously reported by DAP12(-/-) macrophages. Taken together, these data show that TREM-2 is expressed on newly differentiated and alternatively activated macrophages and functions to restrain macrophage activation.
Turnbull
Isaiah R
IR
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gilfillan
Susan
S
Cella
Marina
M
Aoshi
Taiki
T
Miller
Mark
M
Piccio
Laura
L
Hernandez
Maristela
M
Colonna
Marco
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D019169:Jurkat Cells; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; C498716:Trem2 protein, mouse