TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria.
Phagocytosis, which is essential for the immune response to pathogens, is initiated by specific interactions between pathogens and cell surface receptors expressed by phagocytes. This study identifies triggering receptor expressed on myeloid cells 2 (TREM-2) and its signaling counterpart DAP12 as a molecular complex that promotes phagocytosis of bacteria. Expression of TREM-2-DAP12 enables nonphagocytic Chinese hamster ovary cells to internalize bacteria. This function depends on actin cytoskeleton dynamics and the activity of the small guanosine triphosphatases Rac and Cdc42. Internalization also requires src kinase activity and tyrosine phosphorylation. In bone marrow-derived macrophages, phagocytosis is decreased in the absence of DAP12 and can be restored by expression of TREM-2-DAP12. Depletion of TREM-2 inhibits both binding and uptake of bacteria. Finally, TREM-2-dependent phagocytosis is impaired in Syk-deficient macrophages. This study highlights a novel role for TREM-2-DAP12 in the immune response to bacterial pathogens.
N'Diaye
Elsa-Noah
EN
Macrophage Biology Laboratory, San Francisco VA Medical Center, San Francisco, CA 94121, USA.
Branda
Catherine S
CS
Branda
Steven S
SS
Nevarez
Lisette
L
Colonna
Marco
M
Lowell
Clifford
C
Hamerman
Jessica A
JA
Seaman
William E
WE
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000276:immunology / Q000378:metabolism; D018407:Bacterial Physiological Phenomena; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004926:Escherichia coli / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse; C484963:Tyrobp protein, mouse