Figure 6.

Neutrophils-induced inflammatory mechanisms involved in tissue destruction and bone loss. Neutrophils are recruited in a developmental endothelial locus (Del)-1-induced pathway into the gingival epithelium that fail to encounter the dysbiotic bacteria which invade the gingival connective tissue and interact with different host cells such as dendritic cells and γδ T cells. Host-bacterial interaction results in production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, IL-23, and IL-17. IL-17 has an activating influence on T helper (Th)-17 and B cells, which upon activation increase receptor activator of nuclear factor kappa-B ligand (RANKL) expression, which is also directly activated via the recruited extravasated neutrophils. RANKL drives the activation and maturation of osteoclast precursor to be an active osteoclast that predisposes to bone resorption. The recruited neutrophils have a tissue degradation effect through inducing the expression of matrix metalloproteinases (MMP) and cytotoxic substances such as reactive oxygen species (ROS). The microbial-innate-adaptive cell interactions demonstrate some of the main mechanisms involved in the continuity of inflammation if not resolved, leading to tissue destruction.