CX₃CR1^hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection-Driven Bone Resorption

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.