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Published online
doi:10.1083/jcb.200808080
The Journal of Cell Biology, Vol. 184, No. 2, 215-223
The Rockefeller University Press, 0021-9525 $30.00
© N'Diaye et al.
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TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria



Elsa-Noah N'Diaye1, Catherine S. Branda2, Steven S. Branda2, Lisette Nevarez1, Marco Colonna3, Clifford Lowell4, Jessica A. Hamerman5, and William E. Seaman1

1 Macrophage Biology Laboratory, San Francisco VA Medical Center, San Francisco, CA 94121
2 Sandia National Laboratories, Livermore, CA 94550
3 Washington University School of Medicine, St. Louis, MO 63110
4 University of California, San Francisco, San Francisco, CA 94143
5 Benaroya Research Institute, Seattle, WA 98101

Correspondence to William E. Seaman: bseaman{at}medicine.ucsf.edu

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.

Abbreviations used in this paper: BMDM, bone marrow–derived macrophage; cyto D, cytochalasin D; dn, dominant negative; ITAM, immunoreceptor tyrosine-based activation motif; KD, knockdown; TREM, triggering receptor expressed on myeloid cells; wt, wild type.

© 2009 N'Diaye et al.
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