Abstract
The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, with the capacity to amplify pro-inflammatory cytokine production and regulate apoptosis. Polymorphonuclear neutrophils (PMNs) are the first line of defence against infection, and a major source of TREM-1. Porphyromonas gingivalis is a Gram-negative anaerobe highly implicated in the inflammatory processes governing periodontal disease, which is characterized by the destruction of the tooth-supporting tissues. It expresses a number of virulence factors, including the cysteine proteinases (or gingipains). The aim of this in vitro study was to investigate the effect of P. gingivalis on TREM-1 expression and production by primary human PMNs, and to evaluate the role of its gingipains in this process. After 4 h of challenge, P. gingivalis enhanced TREM-1 expression as identified by quantitative real-time PCR. This was followed by an increase in soluble (s)TREM-1 secretion over a period of 18 h, as determined by ELISA. At this time-point, the P. gingivalis-challenged PMNs exhibited diminished TREM-1 cell-membrane staining, as identified by flow cytometry and confocal laser scanning microscopy. Furthermore engagement of TREM-1, by means of anti-TREM-1 antibodies, enhanced the capacity of P. gingivalis to stimulate interleukin (IL)-8 production. Conversely, antagonism of TREM-1 using a synthetic peptide resulted in reduction of IL-8 secretion. Using isogenic P. gingivalis mutant strains, we identified the Arg-gingipain to be responsible for shedding of sTREM-1 from the PMN surface, whereas the Lys-gingipain had the capacity to degrade TREM-1. In conclusion, the differential regulation of TREM-1 by the P. gingivalis gingipains may present a novel mechanism by which P. gingivalis manipulates the host innate immune response helping to establish chronic periodontal inflammation.
Highlights
Periodontal diseases are the most common inflammatory infections in humans, caused by complex polymicrobial biofilms attaching on the tooth surface and causing inflammation by the tooth-supporting tissues [1]
After 4 h, the wild-type P. gingivalis W50 strain induced a concentration-dependent upregulation of Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) expression, which proved to be significant with MOI 10 and MOI 100 (Figure 1A)
We found that P. gingivalis regulates TREM-1 in Polymorphonuclear neutrophils (PMNs), with potential implications in down-stream inflammatory responses
Summary
Periodontal diseases are the most common inflammatory infections in humans, caused by complex polymicrobial biofilms attaching on the tooth surface and causing inflammation by the tooth-supporting (periodontal) tissues [1]. The balanced relationship between the biofilm microbiota and the host response of periodontal tissues is commensurate with health. Polymorphonuclear neutrophils (PMNs) are the first cells to be recruited to the site of inflammation, in response to the developing subgingival biofilmassociated infections in the periodontal tissues [3,4]. Beyond the protective role against bacterial infections PMN may cause collateral damage to the periodontal tissues. PMNs have been extensively studied for their involvement in the local inflammatory responses to periodontal disease, not much is known on their potential role in the amplification of inflammation
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