Disruption of Monocyte and Macrophage Homeostasis in Periodontitis

Abdulrahman Almubarak, Kranthi Kiran Kishore Tanagala, Panos N. Papapanou, Evanthia Lalla, Fatemeh Momen-Heravi

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122 Citations (Scopus)

Abstract

Monocytes and macrophages are major cellular components of the innate immunity that play essential roles in tissue homeostasis. The contribution of different subsets of monocytes/macrophages to periodontal health and disease has not been fully elucidated. Type 2 diabetes mellitus (T2DM) is a risk factor for periodontitis. We hypothesized that the monocyte/macrophage signaling is perturbed in periodontitis-affected sites versus periodontally healthy sites and that this perturbation plays a critical role in the pathogenesis of periodontitis. Pairs of gingival tissue samples (each from a periodontally healthy and a periodontitis-affected site of the same patient) were harvested from 27 periodontitis patients, with and without T2DM. Each sample was processed to form a single-cell suspension, and a flow-cytometry panel was designed and validated to study monocyte and macrophage phenotypes. In separate experiments, the transcriptional changes associated with a pro-inflammatory phenotype were also examined in monocyte/macrophage subsets obtained from peripheral blood of patients with T2DM versus diabetes-free controls. A significantly higher proportion of intermediate (CD14+CD16+) monocytes was observed in periodontitis-affected tissues compared to healthy tissues. These monocytes overexpressed HLA-DR and PDL1 molecules, suggesting their activated inflammatory status. PDL1 increase was specific to intermediate monocytes. The ratio of M1/M2 macrophages was also significantly higher in periodontally affected sites, signifying an imbalance between inflammatory and repair mechanisms. We found a significantly higher expression of PDL1 in overall monocytes and M1 macrophages in periodontitis-affected sites compared to controls. Importantly, we identified a subpopulation of M1 macrophages present in periodontally affected tissues which expressed high levels of CD47, a glycoprotein of the immunoglobulin family that plays a critical role in self-recognition and impairment of phagocytosis. Analysis of the transcriptional landscape of monocytes/macrophages in gingival tissue of T2DM patients with periodontitis revealed a significant disruption in homeostasis toward a proinflammatory phenotype, elevation of pro-inflammatory transcription factors STAT1 and IRF1, and repression of anti-inflammatory JMJD3 in circulating monocytes. Taken together, our results demonstrate disruption of myeloid-derived cell homeostasis in periodontitis, with or without T2DM, and highlight a potentially significant role of these cell types in its pathogenesis. The impact of macrophage and monocyte signaling pathways on the pathobiology of periodontitis should be further evaluated.

Original languageEnglish
Article number330
JournalFrontiers in Immunology
Volume11
DOIs
Publication statusPublished - Feb 26 2020

Bibliographical note

Publisher Copyright:
© Copyright © 2020 Almubarak, Tanagala, Papapanou, Lalla and Momen-Heravi.

Funding

This research was funded by grants from the Columbia University Irving Medical Center, the Columbia University College of Dental Medicine, and the Irving Institute for Clinical and Translational Research (UL1 TR001873). These studies used the Herbert Irving Comprehensive Cancer Center, Flow Cytometry Shared Resource, funded in part through a Center Grant (P30 CA013696) from the NIH.

FundersFunder number
National Institutes of Health
Institute for Clinical and Translational Research, University of Wisconsin, MadisonUL1 TR001873, P30 CA013696
National Center for Advancing Translational SciencesUL1TR001873
College of Dental Medicine, Columbia University
Irving Medical Center, Columbia University

    ASJC Scopus Subject Areas

    • Immunology and Allergy
    • Immunology

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