Gingival lymphatic drainage protects against Porphyromonas gingivalis-induced bone loss in mice

Periodontitis is characterized by tissue destruction and bone loss mainly due to inflammatory responses after bacterial challenge of the gingiva. Gingiva is supplied with lymphatics that drain interstitial fluid and transport immune cells to the lymph nodes for antigen presentation; yet, the role of lymphatics in periodontal disease development is unknown. To investigate the lymphatic function after periodontal infection, we used K14-VEGF receptor 3-Ig (K14) mice that lack lymphatics in gingiva. Mice were orally infected with human Porphyromonas gingivalis and observed for 42 days. The infected K14 mice developed significantly more bone loss than the wild-type mice, and were associated with an increased number of macrophages and major histocompatibility complex class II antigen-presenting cells in the bone resorptional areas. The infected transgenic mice expressed a significant higher periodontal level of several proinflammatory cytokines, whereas the plasma level of P. gingivalis IgG was significantly lower than in the wild-type mice. No differences were found in immune cell distribution in draining lymph nodes between the strains. Our results show that a strong periodontal inflammatory response and a weakened systemic humoral B-cell response took place in K14 mice after infection. We conclude that gingival lymphatics protect against P. gingivalis-induced periodontitis, and we speculate that they are critical in the protection by clearance of infection and by promotion of humoral immune responses.