Porphyromonas gingivalis promotes lipid droplet-mediated microglial dysfunction

Area of Science:

• Neuroimmunology
• Microbial Pathogenesis
• Neurodegenerative Diseases

Background:

• Periodontitis and Alzheimer's disease (AD) share a strong association, but underlying mechanisms are unclear.
• Microglia, the brain's immune cells, show lipid droplet accumulation and dysfunction in neurodegenerative disorders like AD.
• Porphyromonas gingivalis (Pg) is a key pathogen in periodontitis.

Purpose of the Study:

• To investigate if Porphyromonas gingivalis (Pg) induces lipid droplet (LD) accumulation in microglia.
• To determine the impact of Pg-induced LD accumulation on microglial function.
• To explore the role of lipid metabolism in microglial dysfunction during periodontitis.

Main Methods:

• Infection of BV2 microglial cells and microglia from Pg-infected App KI mice with Porphyromonas gingivalis.
• Assessment of lipid droplet accumulation, reactive oxygen species (ROS) production, and phagocytic ability.
• Pharmacological inhibition of lipid droplet synthesis using a triglyceride synthesis inhibitor.

Main Results:

• Pg infection robustly increased LD accumulation in microglia.
• Pg-induced LD buildup correlated with increased ROS production, impaired phagocytosis, and altered microglial activation.
• Inhibiting LD synthesis reversed these functional deficits, highlighting lipid metabolism's role.

Conclusions:

• Porphyromonas gingivalis promotes lipid droplet accumulation in microglia, contributing to their dysfunction.
• This microglial metabolic alteration exacerbates oxidative stress and impairs phagocytosis, potentially accelerating Alzheimer's disease progression.
• Targeting lipid metabolism may offer a therapeutic strategy for periodontitis-associated neuroinflammation.