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Published in: Journal of Neuroinflammation 1/2023

Open Access 01-12-2023 | Gingival Diseases | Research

Microglial cell response to experimental periodontal disease

Authors: Rawan Almarhoumi, Carla Alvarez, Theodore Harris, Christina M. Tognoni, Bruce J. Paster, Isabel Carreras, Alpaslan Dedeoglu, Alpdogan Kantarci

Published in: Journal of Neuroinflammation | Issue 1/2023

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Abstract

Objectives

Microglial activation is critical for modulating the neuroinflammatory process and the pathological progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglia are involved in forming barriers around extracellular neuritic plaques and the phagocytosis of β-amyloid peptide (Aβ). In this study, we tested the hypothesis that periodontal disease (PD) as a source of infection alters inflammatory activation and Aβ phagocytosis by the microglial cells.

Methods

Experimental PD was induced using ligatures in C57BL/6 mice for 1, 10, 20, and 30 days to assess the progression of PD. Animals without ligatures were used as controls. Maxillary bone loss and local periodontal tissue inflammation associated with the development of PD were confirmed by morphometric bone analysis and cytokine expression, respectively. The frequency and the total number of activated microglia (CD45+ CD11b+ MHCII+) in the brain were analyzed by flow cytometry. Mouse microglial cells (1 × 105) were incubated with heat-inactivated bacterial biofilm isolated from the ligatures retrieved from the teeth or with Klebsiella variicola, a relevant PD-associated bacteria in mice. Expression of pro-inflammatory cytokines, toll-like receptors (TLR), and receptors for phagocytosis was measured by quantitative PCR. The phagocytic capacity of microglia to uptake β-amyloid was analyzed by flow cytometry.

Results

Ligature placement caused progressive periodontal disease and bone resorption that was already significant on day 1 post-ligation (p < 0.05) and continued to increase until day 30 (p < 0.0001). The severity of periodontal disease increased the frequency of activated microglia in the brains on day 30 by 36%. In parallel, heat-inactivated PD-associated total bacteria and Klebsiella variicola increased the expression of TNFα, IL-1β, IL-6, TLR2, and TLR9 in microglial cells (1.6-, 83-, 3.2-, 1.5-, 1.5-fold, respectively p < 0.01). Incubation of microglia with Klebsiella variicola increased the Aβ-phagocytosis by 394% and the expression of the phagocytic receptor MSR1 by 33-fold compared to the non-activated cells (p < 0.0001).

Conclusions

We showed that inducing PD in mice results in microglia activation in vivo and that PD-associated bacteria directly promote a pro-inflammatory and phagocytic phenotype in microglia. These results support a direct role of PD-associated pathogens in neuroinflammation.
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Metadata
Title
Microglial cell response to experimental periodontal disease
Authors
Rawan Almarhoumi
Carla Alvarez
Theodore Harris
Christina M. Tognoni
Bruce J. Paster
Isabel Carreras
Alpaslan Dedeoglu
Alpdogan Kantarci
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02821-x

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