IADR Abstract Archives
A Novel Porphyromonas Gingivalis Human Challenge Model
Objectives: Animal experimental evidence suggests P.gingivalis as a keystone pathogen in the development of periodontitis and its links with systemic diseases. Limited or no evidence exists in humans. The aim of this research was to develop a novel experimental model of P.gingivalis challenge in humans.
Methods: Ten healthy volunteers received two intradermal UV-killed P.gingivalis injections on the forearms followed by the formation of artificial blister. Serial increasing doses of P.gingivalis were evaluated by blood perfusion, skin temperature, and cellular analyses of the blister exudate were conducted using polychromatic flow cytometric analysis. The host response to the challenge was monitored by forehead temperature, full blood count, and serum C-Reactive Protein (CRP) levels.
Results: P.gingivalis challenge demonstrated a visible forearm response with increased blood flow peaking at 24 hours (p<0.001) and fading at 48 hours, whilst the local site’s temperature remained unchanged. The local cellular response (4 hours post-injection) was characterized by neutrophil influx (p<0.001) and late T lymphocyte accumulation (48 hours). Consistent alterations of blister fluid-derived myeloid (monocyte subsets and dendritic cells) and lymphoid cells (CD4, CD8, B lymphocytes, and NK cells) were observed between 4 and 48 hours post-injection. No substantial alteration in forehead temperature and serum CRP level were noted whilst increased white blood cell and neutrophil counts (p<0.01 for both) that were observed at the onset of inflammation returned to baseline at 48 hours.
Conclusions: A novel human-challenge model of UV-killed P.gingivalis injection was developed to induce localized and transient inflammatory responses. A self-contained innate immune response reaction was safely reproduced. The model holds promise in evaluating host-pathogens interaction in periodontitis and systemic health in humans.
Methods: Ten healthy volunteers received two intradermal UV-killed P.gingivalis injections on the forearms followed by the formation of artificial blister. Serial increasing doses of P.gingivalis were evaluated by blood perfusion, skin temperature, and cellular analyses of the blister exudate were conducted using polychromatic flow cytometric analysis. The host response to the challenge was monitored by forehead temperature, full blood count, and serum C-Reactive Protein (CRP) levels.
Results: P.gingivalis challenge demonstrated a visible forearm response with increased blood flow peaking at 24 hours (p<0.001) and fading at 48 hours, whilst the local site’s temperature remained unchanged. The local cellular response (4 hours post-injection) was characterized by neutrophil influx (p<0.001) and late T lymphocyte accumulation (48 hours). Consistent alterations of blister fluid-derived myeloid (monocyte subsets and dendritic cells) and lymphoid cells (CD4, CD8, B lymphocytes, and NK cells) were observed between 4 and 48 hours post-injection. No substantial alteration in forehead temperature and serum CRP level were noted whilst increased white blood cell and neutrophil counts (p<0.01 for both) that were observed at the onset of inflammation returned to baseline at 48 hours.
Conclusions: A novel human-challenge model of UV-killed P.gingivalis injection was developed to induce localized and transient inflammatory responses. A self-contained innate immune response reaction was safely reproduced. The model holds promise in evaluating host-pathogens interaction in periodontitis and systemic health in humans.