High-Fat Diet Reprograms the Periapical Immune Landscape in a Mouse Model of Apical Periodontitis: A Spatial...

Area of Science:

• Immunology
• Endodontics
• Metabolic disease

Background:

• Apical periodontitis (AP) involves inflammation of periapical tissues due to endodontic infection.
• Systemic metabolic issues, like high-fat diet (HFD)-induced dysmetabolism, can worsen AP.
• Chronic HFD exposure's impact on periapical myeloid cells and lesion characteristics in AP requires investigation.

Purpose of the Study:

• To investigate how chronic HFD exposure affects periapical myeloid cell states in AP.
• To analyze changes in apical lesion characteristics under HFD conditions.
• To utilize spatially resolved transcriptomics to map these alterations in a mouse model.

Main Methods:

• Mice were fed either normal chow (NC) or 60% HFD for 18 weeks.
• AP was induced in the first molars after 14 weeks of diet.
• Periapical tissues were analyzed using spatial transcriptomics (10× Genomics Xenium) focusing on neutrophils and macrophages.

Main Results:

• HFD mice showed increased body weight, higher fasting glucose, and significantly larger apical lesion volumes compared to NC mice.
• Spatial transcriptomics revealed HFD-shifted myeloid cells towards lipid handling and inflammasome activity, while NC maintained antimicrobial signatures.
• Within lesions, HFD was linked to foam cell-like macrophages and reduced neutrophil bactericidal function, unlike NC lesions.

Conclusions:

• Chronic HFD reprograms periapical immunity from defense to lipid-driven inflammation, exacerbating bone loss in AP.
• Spatial transcriptomics is a valuable tool for studying immunometabolic pathways in endodontic disease.
• Findings suggest potential therapeutic targets for AP in patients with metabolic compromise.