TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells.
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.
Quan
D N
DN
Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, California, USA.
Cooper
M D
MD
Potter
J L
JL
Roberts
M H
MH
Cheng
H
H
Jarvis
G A
GA
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005187:Fallopian Tubes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction
D001425:Bacterial Outer Membrane Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; C424124:TREM-2a receptor; C023023:lipid-linked oligosaccharides; C090348:Opa protein, Neisseria