Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human β-defensin-2

Abstract

Oral epithelia are constantly exposed to non-pathogenic (commensal) bacteria, but generally remain healthy and uninflamed. Fusobacterium nucleatum, an oral commensal bacterium, strongly induces human beta-defensin-2 (hBD2), an antimicrobial and immunomodulatory peptide, in gingival epithelial cells (GECs). hBD2 is also expressed in normal oral tissue leading to the hypothesis that oral epithelia are in an activated state with respect to innate immune responses under normal in vivo conditions. In order to test this hypothesis, global gene expression was evaluated in GECs in response to stimulation by an F. nucleatum cell wall (FnCW) preparation and to hBD2 peptide. FnCW treatment altered 829 genes, while hBD2 altered 209 genes (P<0.005, ANOVA). Many induced genes were associated with the gene ontology categories of immune responses and defence responses. Consistent with the hypothesis, similar responses were activated by commensal bacteria and hBD2. These responses included up-regulation of common antimicrobial effectors and chemokines, and down-regulation of proliferation markers. In addition, FnCW up-regulated multiple protease inhibitors, and suppressed NF-kappaB function and the ubiquitin/proteasome system. These global changes may protect the tissue from inflammatory damage. Both FnCW and hBD2 also up-regulated genes that may enhance the epithelial barrier. The findings suggest that both commensal bacteria and hBD2 activate protective responses of GECs and play an important role in immune modulation in the oral cavity.