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

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Abstract

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.

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Acknowledgments

Pablo Veloso thanks the fellowship CONICYT 21171640, from the Chilean Government and B. Pesce (PhD.) by supporting flow cytometric procedures at the MED.UCHILE-FACS Laboratory from Biomedical Sciences Institute, School of Medicine of University of Chile, Santiago de Chile.

Funding

The work was supported by FONDECYT grant number 1160741.

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Authors and Affiliations

  1. Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, 8380000, Chile

    Pablo Veloso, Alejandra Fernández, Claudia Terraza-Aguirre, Carla Álvarez, Rolando Vernal & Marcela Hernández

  2. Faculty of Dentistry, Universidad Andres Bello, Santiago, 8370133, Chile

    Alejandra Fernández

  3. Department of Conservative Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago, 8380000, Chile

    Rolando Vernal

  4. Institute of Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, 8380000, Chile

    Alejandro Escobar

  5. Department of Pathology and Oral Medicine, Faculty of Dentistry, Universidad de Chile, Av. Sergio Livingstone 943, 8380492 Independencia, Santiago, 8380000, Chile

    Marcela Hernández

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  1. Pablo Veloso
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Correspondence to Marcela Hernández.

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Veloso, P., Fernández, A., Terraza-Aguirre, C. et al. Macrophages skew towards M1 profile through reduced CD163 expression in symptomatic apical periodontitis. Clin Oral Invest 24, 4571–4581 (2020). https://doi.org/10.1007/s00784-020-03324-2

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