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PMID: 19171755 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria.

The Journal of cell biology ·Vol. 184 ·No. 2 ·2009-01-26 ·Pages 215-23

N'Diaye EN, Branda CS, Branda SS, Nevarez L, Colonna M, Lowell C, Hamerman JA, Seaman WE

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism Animals Bacteria/immunology,metabolism Bacterial Physiological Phenomena CHO Cells Cells, Cultured Cricetinae Cricetulus Escherichia coli/metabolism Membrane Glycoproteins/metabolism Mice Mice, Knockout Myeloid Cells/immunology,metabolism Phagocytosis/immunology Receptors, Immunologic/metabolism Staphylococcus aureus/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Membrane Glycoproteins Receptors, Immunologic Trem2 protein, mouse Tyrobp protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
N'Diaye Elsa-Noah
Macrophage Biology Laboratory, San Francisco VA Medical Center, San Francisco, CA 94121, USA.
Branda Catherine S
Branda Steven S
Nevarez Lisette
Colonna Marco
Lowell Clifford
Hamerman Jessica A
Seaman William E
References (36)
36 references, click to expand
  1. Phagosomal maturation, acidification, and inhibition of bacterial growth in nonphagocytic cells transfected with FcgammaRIIA receptors.
    J Biol Chem. 1999 Oct 1;274(40):28436-44 PMID: 10497205
  2. Src and Syk kinases: key regulators of phagocytic cell activation.
    Trends Immunol. 2005 Apr;26(4):208-14 PMID: 15797511
  3. Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production.
    Blood. 2005 Oct 1;106(7):2543-50 PMID: 15956283
  4. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2.
    J Exp Med. 2005 Feb 21;201(4):647-57 PMID: 15728241
  5. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12.
    J Immunol. 2006 Aug 15;177(4):2051-5 PMID: 16887962
  6. Activating and inhibitory functions of DAP12.
    Nat Rev Immunol. 2007 Feb;7(2):155-61 PMID: 17220916
  7. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens.
    Nature. 1999 Oct 21;401(6755):811-5 PMID: 10548109
  8. The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function.
    Immunol Today. 2000 Dec;21(12):611-4 PMID: 11114420
  9. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes.
    J Exp Med. 1983 Dec 1;158(6):2016-23 PMID: 6227677
  10. The TREM receptor family and signal integration.
    Nat Immunol. 2006 Dec;7(12):1266-73 PMID: 17110943
  11. Integrative studies put cell wall synthesis on the yeast functional map.
    Curr Opin Microbiol. 2004 Dec;7(6):617-23 PMID: 15556034
  12. Molecular mechanisms of phagocytic uptake in mammalian cells.
    Cell Mol Life Sci. 2008 Jul;65(13):1957-76 PMID: 18322649
  13. A requirement for phosphatidylinositol 3-kinase in pseudopod extension.
    J Biol Chem. 1999 Jan 15;274(3):1240-7 PMID: 9880492
  14. The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12.
    Infect Immun. 2008 Jun;76(6):2439-47 PMID: 18391000
  15. Syk expression and novel function in a wide variety of tissues.
    Biochem Biophys Res Commun. 2001 Nov 2;288(3):495-8 PMID: 11676469
  16. The Syk protein tyrosine kinase is essential for Fcgamma receptor signaling in macrophages and neutrophils.
    Mol Cell Biol. 1998 Jul;18(7):4209-20 PMID: 9632805
  17. Regulation of phagocytosis by Rho GTPases.
    Curr Top Microbiol Immunol. 2005;291:43-60 PMID: 15981459
  18. Phagocytosis: at the crossroads of innate and adaptive immunity.
    Annu Rev Cell Dev Biol. 2005;21:511-27 PMID: 16212505
  19. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs.
    Nat Immunol. 2006 Dec;7(12):1326-33 PMID: 17086186
  20. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes.
    J Exp Med. 1982 Oct 1;156(4):1149-64 PMID: 7153708
  21. PI3K class IB pathway in neutrophils.
    Sci STKE. 2007 Oct 09;2007(407):cm3 PMID: 17925574
  22. Cutting edge: TREM-2 attenuates macrophage activation.
    J Immunol. 2006 Sep 15;177(6):3520-4 PMID: 16951310
  23. Plat-E: an efficient and stable system for transient packaging of retroviruses.
    Gene Ther. 2000 Jun;7(12):1063-6 PMID: 10871756
  24. Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling.
    Nature. 2008 Jun 12;453(7197):935-9 PMID: 18432193
  25. CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion.
    Curr Biol. 1997 Jun 1;7(6):408-17 PMID: 9197241
  26. A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages.
    J Exp Med. 1997 Oct 6;186(7):1027-39 PMID: 9314552
  27. Phagocytosis.
    Bioessays. 1995 Feb;17(2):109-17 PMID: 7748161
  28. Nonopsonic binding of Mycobacterium tuberculosis to human complement receptor type 3 expressed in Chinese hamster ovary cells.
    Infect Immun. 1996 Dec;64(12):5373-83 PMID: 8945590
  29. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.
    Science. 1998 Nov 27;282(5394):1717-21 PMID: 9831565
  30. Mechanisms of phagocytosis in macrophages.
    Annu Rev Immunol. 1999;17:593-623 PMID: 10358769
  31. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.
    Immunity. 2000 Sep;13(3):345-53 PMID: 11021532
  32. Pattern recognition by TREM-2: binding of anionic ligands.
    J Immunol. 2003 Jul 15;171(2):594-9 PMID: 12847223
  33. Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcgammaR, phagocytosis.
    Curr Biol. 2002 Aug 20;12(16):1413-18 PMID: 12194823
  34. DAP12: an adapter protein with dual functionality.
    Immunol Rev. 2006 Dec;214:118-29 PMID: 17100880
  35. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages.
    Blood. 2004 Dec 15;104(13):4038-45 PMID: 15304394
  36. The alliance for cellular signaling plasmid collection: a flexible resource for protein localization studies and signaling pathway analysis.
    Mol Cell Proteomics. 2007 Mar;6(3):413-24 PMID: 17192258
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
Published
2009-01-26
Pages
215-23
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2654305
Subset
IM
Grants
NIGMS NIH HHS · GM 062114 · United States
NIGMS NIH HHS · U54 GM062114 · United States
NCI NIH HHS · R01 CA 87922 · United States
NCI NIH HHS · R01 CA087922 · United States
NIAID NIH HHS · R01 AI073441 · United States
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