Porphyromonas gingivalis triggers microglia activation and neurodegenerative processes through NOX4

Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria P. gingivalis and microglia cells, and to unravel if these interactions could contribute to Alzheimer’s pathology. Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria P. gingivalis and microglia cells, and to unravel if these interactions could contribute to Alzheimer’s pathology. We found, through microarray analysis, that stimulation of microglia cells with P. gingivalis resulted in upregulation of several Alzheimer´s disease associated genes, including NOX4. We also showed that P. gingivalis LPS mediated ROS production and IL-6 and IL-8 induction via NOX4 in microglia. The viability of neurons was shown to be reduced by conditioned media from microglia cells stimulated with P. gingivalis LPS, and that the reduction was NOX4 dependent. The levels of total and phosphorylated Tau in neurons were increased by conditioned media from microglia cells stimulated with P. gingivalis or LPS. This increase was NOX4 dependent. In summary our findings give us a potential mechanistic explanation of how the periodontal pathogen P. gingivalis could trigger or exacerbate AD pathogenesis. HMC3 cells were stimulated with P. gingivalis strains W50, E8 and K1A (MOI 10) for 24 hours and the gene expression was evaluated.