title: CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection-Driven Bone Resorption.
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.
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Steinmetz
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Shifra
authors.initials: S
authors.lastname: Hoch
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Avniel-Polak
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Gavish
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Luba
authors.initials: L
authors.lastname: Eli-Berchoer
authors.affiliation: Department of Periodontology, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Wilensky
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nussbaum
mesh_terms: D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology*; D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000382:microbiology; D000073883:CX3C Chemokine Receptor 1; D054884:Host-Pathogen Interactions / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology / Q000472:pathogenicity; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine
keywords: monocytes; neutrophils; periodontitis; phagocytosis