Macrophages skew towards M1 profile through reduced CD163 expression in symptomatic apical periodontitis

Objectives: To explore the macrophage profiles in symptomatic and asymptomatic forms of AP through phenotypic and functional analyses. Material and methods: Cross-sectional study. Apical tissue/lesion samples were collected from patients with clinical diagnosis of AAP (n = 51) or SAP (n = 45) and healthy periodontal ligament (HPL) from healthy patients as controls (n = 14), all with indication of tooth extraction. Samples were digested, cells were stained for CD14, M1 (CD64, CD80), and M2 (CD163, CD206) phenotypic surface markers and analyzed by flow cytometry. Functional cytokine profiles L-6, IL-12, TNF-α, IL-23 (M1), IL-10, and TGF-β (M2) were determined by qPCR. Results: Higher macrophage M1/M2 ratio (CD64⁺CD80⁺/CD163⁺CD206⁺) along with lower CD163 mean fluorescence intensity (MFI) were found in SAP compared to AAP and controls (p < 0.05). IL-6, IL-12, TNF-α, IL-23 (M1), and IL-10 mRNA (M2) were upregulated, whereas TGF-β mRNA (M2) was downregulated in apical lesions compared to controls. Specifically, IL-6 and IL-23 (M1) were upregulated in SAP compared with AAP and controls (p < 0.05). The data were analyzed with Kruskal-Wallis test. Conclusions: Macrophages exhibited a polarization switch towards M1 in AL. SAP exhibited a reduced M2 differentiation profile based on a reduction of CD163 expression levels in SAP over AAP. Specifically, IL-6 and IL-23 were augmented SAP over AAP, suggesting a role in the severity of apical lesions. Clinical relevance: Deciphering the macrophage polarization and functions in apical periodontitis can contribute to explain AP dynamics, its clinical presentation and systemic impact.