The epithelial cell rests of Malassez (ERM) are located within the periodontal ligament. They are reportedly involved in maintaining homeostasis, particularly with regards to the thickness of the periodontal ligament. Their role in apical periodontitis lesions remains unclear, however. This study investigated the response of ERM to infection with Porphyromonas gingivalis. After being infected, the morphology of the P. gingivalis-infected cells was observed using confocal laser-scanning microscopy. The gene expression of P. gingivalis-infected and uninfected cells was investigated by RNA-sequencing analysis. Morphological observation showed the invasion and adhesion of P. gingivalis to the surface of ERM. The RNA analysis showed that the gene expression profile significantly differed between the infected and uninfected cells. At an expression level of ≥2 and false discovery rate of <
0.1, the infected cells showed a decrease in 99 genes and an increase in 6 compared with in the non-infected cells. Most of the upregulated genes were unique to epithelial cells, such as endothelial cell-specific molecules and cytokeratin 5
the upregulated genes were associated with the immune response, however. These results indicate that ERM upregulate genes associated with epithelial cells and suppress those associated with the immune response following P. gingivalis infection.