title: Immune and regulatory functions of neutrophils in inflammatory bone loss.
abstract: Although historically viewed as merely anti-microbial effectors in acute infection or injury, neutrophils are now appreciated to be functionally versatile with critical roles also in chronic inflammation. Periodontitis, a chronic inflammatory disease that destroys the tooth-supporting gums and bone, is particularly affected by alterations in neutrophil numbers or function, as revealed by observations in monogenic disorders and relevant mouse models. Besides being a significant debilitating disease and health burden in its own right, periodontitis is thus an attractive model to dissect uncharted neutrophil-associated (patho)physiological pathways. Here, we summarize recent evidence that neutrophils can contribute to inflammatory bone loss not only through the typical bystander injury dogma but intriguingly also through their absence from the affected tissue, where they normally perform important immunomodulatory functions. Moreover, we discuss recent advances in the interactions of neutrophils with the vascular endothelium and - upon extravasation - with bacteria, and how the dysregulation of these interactions leads to inflammatory tissue damage. Overall, neutrophils have both protective and destructive roles in periodontitis, as they are involved in both the maintenance of periodontal tissue homeostasis and the induction of inflammatory bone loss. This highlights the importance of developing approaches that promote or sustain a fine balance between homeostatic immunity and inflammatory pathology.
authors.affiliation: University of Pennsylvania, Penn Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA. Electronic address: geoh@upenn.edu.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: Oral Immunity and Inflammation Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.
authors.forename: Niki M
authors.initials: NM
authors.lastname: Moutsopoulos
authors.affiliation: University of Pennsylvania, Penn Dental Medicine, Department of Preventive and Restorative Sciences, Division of Pediatric Dentistry, Philadelphia, PA 19104, USA.
authors.forename: Evlambia
authors.initials: E
authors.lastname: Hajishengallis
authors.affiliation: Technische Universität Dresden, Faculty of Medicine, Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001862:Bone Resorption / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010518:Periodontitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology
keywords: Bone loss; Del-1; Inflammation; Leukocyte-adhesion deficiency; Neutrophils; Periodontitis