A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response.
Triggering receptor expressed on myeloid cells (TREM)-1 is a cell surface molecule expressed on neutrophils and monocytes implicated in the propagation of the inflammatory response. To further characterize the function of this molecule in different phases of the immune response, we examined TREM-1 in the context of host defense against microbial pathogens. In primary human monocytes TREM-1 activation did not trigger innate antimicrobial pathways directed against intracellular Mycobacterium tuberculosis, and only minimally improved phagocytosis. However, activation of TREM-1 on monocytes did drive robust production of proinflammatory chemokines such as macrophage inflammatory protein-1alpha and IL-8. Engagement of TREM-1 in combination with microbial ligands that activate Toll-like receptors also synergistically increased production of the proinflammatory cytokines TNF-alpha and GM-CSF, while inhibiting production of IL-10, an anti-inflammatory cytokine. Expression of TREM-1 was up-regulated in response to TLR activation, an effect further enhanced by GM-CSF and TNF-alpha but inhibited by IL-10. Functionally, primary monocytes differentiated into immature dendritic cells following activation through TREM-1, evidenced by higher expression of CD1a, CD86, and MHC class II molecules. These cells had an improved ability to elicit T cell proliferation and production of IFN-gamma. Our data suggest that activation of TREM-1 on monocytes participates during the early-induced and adaptive immune responses involved in host defense against microbial challenges.
Bleharski
Joshua R
JR
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Kiessler
Viviane
V
Buonsanti
Cecilia
C
Sieling
Peter A
PA
Stenger
Steffen
S
Colonna
Marco
M
Modlin
Robert L
RL
D001770:Blood Bactericidal Activity / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015854:Up-Regulation / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1