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CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection-Driven Bone Resorption
Orit Steinmetz1, Shifra Hoch1, Shani Avniel-Polak1
1Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
Abstract:
Porphyromonas gingivalis,an anaerobic bacterium strongly linked to infection-driven inflammatory bone erosion, thrives within a highly inflamed milieu and disseminates to distant sites, such as atherosclerotic plaque. We examined the role of monocyte/macrophages in determining the outcome of infection with P. gingivalis. Surprisingly, transient monocyte/macrophage depletion led to greatly improved clearance of P. gingivalis. The chemokine receptors CCR2 and CX3CR1 play a major role in monocyte recruitment and differentiation to Ly6C(hi) vs CX3CR1(hi) subsets, respectively. To determine the contribution of particular monocyte/macrophage subsets to bacterial survival, we challenged chemokine receptor knockout mice and found that P. gingivalis clearance is significantly improved in the absence of CX3CR1. CX3CR1(hi) monocyte/macrophages promote P. gingivalis survival by downregulating neutrophil phagocytosis. Furthermore, CX3CR1 knockout mice resist bone resorption in the oral cavity following challenge with P. gingivalis Our findings provide an explanation for bacterial coexistence alongside an activate neutrophil infiltrate.
Insights
Porphyromonas gingivalis infection clearance improved with monocyte/macrophage depletion. Absence of CX3CR1 enhances bacterial clearance and reduces bone erosion by modulating neutrophil activity.
Area of Science:
- Microbiology
- Immunology
- Periodontology
Background:
- Porphyromonas gingivalis is linked to inflammatory bone erosion and systemic dissemination.
- Monocyte/macrophages play a critical role in infection outcomes.
- Chemokine receptors like CCR2 and CX3CR1 regulate monocyte subsets.
Purpose of the Study:
- To investigate the role of monocyte/macrophage subsets in P. gingivalis infection.
- To determine the impact of CX3CR1 on bacterial clearance and bone resorption.
Main Methods:
- Transient depletion of monocytes/macrophages.
- Utilizing chemokine receptor knockout mouse models (CCR2, CX3CR1).
- Assessing P. gingivalis clearance, neutrophil phagocytosis, and oral bone resorption.
Main Results:
- Transient monocyte/macrophage depletion significantly improved P. gingivalis clearance.
- Absence of CX3CR1 led to enhanced bacterial clearance and resistance to bone resorption.
- CX3CR1(hi) monocyte/macrophages were found to promote P. gingivalis survival by downregulating neutrophil phagocytosis.
Conclusions:
- CX3CR1-expressing monocyte/macrophages are crucial for P. gingivalis survival and pathogenesis.
- Targeting CX3CR1 may offer a therapeutic strategy against P. gingivalis-associated bone loss.
- This study elucidates the complex interplay between P. gingivalis, host immune cells, and inflammatory bone erosion.
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