title: Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis.
abstract: Porphyromonas gingivalis, is a Gram-negative obligate oral anaerobic bacterium highly implicated in periodontal disease, the most prevalent chronic inflammatory disease, but recent evidence also indicates a potential contribution to systemic inflammation. The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which, along with its adaptor signalling molecule DAP12, is involved in immune response to bacterial and fungal infections, particularly by amplifying the production of pro-inflammatory cytokines by the host. The aim of the present study was to investigate the effect of P. gingivalis on the expression of the TREM-1/DAP12 pathway, as well as its engagement in pro-inflammatory cytokine production, by the myelomonocytic cell line MonoMac-6. P. gingivalis enhanced TREM-1 gene expression by the cells, concomitantly to an increase of soluble TREM-1 secretion. Engagement of TREM-1, by introducing anti-TREM-1 to the experimental system, resulted in further potentiation of the pro-inflammatory responses to P. gingivalis, as evaluated by a further enhancement of interleukin (IL)-1β and IL-6 secretion. On the contrary, the synthetic TREM-1 antagonist LP17 reduced the P. gingivalis-induced IL-1β and IL-6 secretion by approximately 50%. In conclusion, the putative periodontal pathogen P. gingivalis can positively regulate the expression of the TREM-1/DAP12 pathway in monocytic cells. Moreover, engagement of TREM-1 can further potentiate the pro-inflammatory responses to P. gingivalis infection. This effect may contribute not only to the pathogenesis of inflammatory periodontal disease, but also to the enhancement of systemic inflammation.
authors.affiliation: Oral Translational Research, Institute of Oral Biology, Center of Dental Medicine, University of Zürich, Plattenstrasse 11, 8032 Zürich, Switzerland. nagihan.bostanci@zzm.uzh.ch
authors.forename: Nagihan
authors.initials: N
authors.lastname: Bostanci
authors.forename: Thomas
authors.initials: T
authors.lastname: Thurnheer
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Belibasakis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C110546:TYROBP protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1