The Presence of Bacteria Within Tissue Provides Insights Into the Pathogenesis of Oral Lichen Planus

Objectives: Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. We postulated that bacterial invasion into the mucosal tissue may be the cause of the immune cell infiltration observed in OLP lesions. The aim of this study is to investigate a potential role of oral bacteria in the pathogenesis of OLP.
Methods: Sections of OLP tissues (n = 36) and normal oral mucosa (n = 10) were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD4, anti-CD8, and anti-macrophage-specific antibodies. The mucosal microbiota from OLP patients (n = 13) and control subjects (n = 18) were analyzed by pyrosequencing. Based on the microbiota data, three bacterial species were chosen, and interaction of the selected bacteria with host cells was studied in vitro.
Results: Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited strong positive correlations with the levels of infiltrated CD4⁺ and CD8⁺ T cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota revealed an increase in invasive bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5.
Conclusions: Our data implicate a novel role of bacteria in the pathogenesis of OLP in which bacteria damage the epithelial barriers, are internalized into epithelial cells and T cells, and induce T cell chemokines. We propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. This result suggests antibiotics as a new therapeutic option of OLP.