title: Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis.
abstract: Once viewed as simply antibacterial effector cells packed with antimicrobials, neutrophils are now increasingly appreciated for their regulatory roles in immunity and inflammation. The homeostatic regulation of neutrophils is thus crucial for optimal operation of the immune system. An attractive model to understand mechanistically the role of neutrophils is periodontitis, an oral inflammatory disease that is particularly sensitive to neutrophil alterations in numbers or function. The recruitment and proper activation of neutrophils are largely dependent on leukocyte integrins and complement. This review discusses how these processes are affected by host genetic or microbial factors leading to the development of periodontitis. For instance, both hypo- and hyper-recruitment of neutrophils as a result of deficiencies in the expression of β2 integrins or their negative regulators, respectively, causes unwarranted IL-17-dependent inflammatory bone loss. Moreover, microbial hijacking of C5aR (CD88) signaling in neutrophils impairs their antimicrobial function while promoting destructive inflammatory responses. These studies not only support the concept that neutrophil homeostasis is key to periodontal health but also reveal promising, new therapeutic targets as discussed in the review.
authors.affiliation: Departments of *Microbiology and Preventive and Restorative Sciences, Division of Pediatric Dentistry, Penn Dental Medicine, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and Technische Universität Dresden, Faculty of Medicine, Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany geoh@upenn.edu.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: Departments of *Microbiology and Preventive and Restorative Sciences, Division of Pediatric Dentistry, Penn Dental Medicine, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and 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
authors.affiliation: Departments of *Microbiology and Preventive and Restorative Sciences, Division of Pediatric Dentistry, Penn Dental Medicine, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and Technische Universität Dresden, Faculty of Medicine, Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany.
authors.forename: Evlambia
authors.initials: E
authors.lastname: Hajishengallis
authors.affiliation: Departments of *Microbiology and Preventive and Restorative Sciences, Division of Pediatric Dentistry, Penn Dental Medicine, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and Technische Universität Dresden, Faculty of Medicine, Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
mesh_terms: D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010518:Periodontitis / Q000276:immunology*
keywords: Del-1; IL-17; complement; integrins; leukocyte adhesion deficiency