Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States.
Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD (cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state.
Department of Dentistry, Matrix Dynamics Group, University of Toronto, Toronto, Canada.
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N
Fine
Department of Dentistry, Matrix Dynamics Group, University of Toronto, Toronto, Canada.
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S
Hassanpour
Department of Dentistry, Matrix Dynamics Group, University of Toronto, Toronto, Canada.
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A
Borenstein
Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA, USA Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
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C
Sima
Department of Dentistry, Matrix Dynamics Group, University of Toronto, Toronto, Canada.
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Oveisi
Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
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Scholey
Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
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Cherney
Department of Dentistry, Matrix Dynamics Group, University of Toronto, Toronto, Canada michael.glogauer@utoronto.ca.
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Glogauer
D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D009055:Mouth / Q000166:cytology / Q000382:microbiology; D009504:Neutrophils / Q000473:pathology*; D010510:Periodontal Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D015415:Biomarkers; D017382:Reactive Oxygen Species
cell degranulation; chronic periodontitis; immunologic surface markers; inflammation; neutrophil extracellular traps; reactive oxygen species