TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells

Mucosal Immunol. 2008 May;1(3):229-38. doi: 10.1038/mi.2008.1. Epub 2008 Mar 5.


Triggering receptor expressed on myeloid cells-2 (TREM-2) is an innate immune receptor that initiates cellular activation upon ligation. In this study, we examined the interaction of TREM-2 with Neisseria gonorrhoeae using murine TREM-2A, as it has been reported to recognize bacterial ligands. Using a whole-bacteria enzyme-linked immunosorbent assay (ELISA), TREM-2A bound to all six strains in variable degrees. Far-western blots of gonococcal outer membranes revealed TREM-2A binding to lipooligosaccharide (LOS) and opacity (Opa) protein, with predominant binding to LOS. Binding of TREM-2A to LOS was confirmed by ELISA and surface plasmon resonance. O-deacylation of the lipid A significantly reduced binding. Flow cytometry and reporter cell assays showed that gonococci bound to TREM-2A-transfected cells and induced transmembrane signaling. In humans, TREM-2 was constitutively expressed by genitourinary and fallopian tube epithelial cells, both of which are primary targets of gonococcal invasion. Ligation of TREM-2 by LOS induced interleukin-6 production in HeLa cervical carcinoma cells. To our knowledge, this is the first report of the expression of human TREM-2 by cells deriving from a non-myeloid lineage. We conclude that gonococci can interact with TREM-2 receptors through binding to LOS and Opa protein and initiate cell signaling and cytokine production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Outer Membrane Proteins / immunology
  • Cell Line
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Fallopian Tubes / immunology*
  • Fallopian Tubes / metabolism
  • Fallopian Tubes / microbiology
  • Female
  • Humans
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / immunology*
  • Mice
  • Neisseria gonorrhoeae / immunology*
  • Protein Binding / immunology
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / immunology*
  • Signal Transduction


  • Bacterial Outer Membrane Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • Receptors, Immunologic
  • TREM-2a receptor
  • lipid-linked oligosaccharides
  • Opa protein, Neisseria