Figure 2.

Neutrophils in the oral cavity. Neutrophils can polarize in response to oral microbiota and in disease, advancing or inhibiting disease progression. In oral cancers, N1 tumor-associated neutrophils (TANs) demonstrate anti-tumorigenic behaviors while N2 TANs are pro-tumorigenic, producing angiogenic factors and suppressing the antitumor immune response. Differentiation to the N1 or N2 phenotype is largely driven by TGF−β, which skews differentiation toward the N2 phenotype. Low-density neutrophils (LDNs) correlate with disease progression. They preferentially propagate in cancer and have a T-cell suppressive function, while proinflammatory LDNs are found in cases of autoimmunity. In addition, there is a subset of oral neutrophils that present with a significant increase in T cell receptor (TCR) expression and are recruited at high rates to sites of inflammation; however, their exact function is unknown. Increased neutrophil recruitment can contribute to the inflammation and alveolar bone loss characteristic of periodontal disease via production of ROS, pro-inflammatory cytokines, and degranulation. Furthermore, individuals with defective neutrophil recruitment or function due to genetic abnormalities are more susceptible to severe periodontal disease.