New developments in neutrophil biology and periodontitis

Abstract

Neutrophils have been historically associated with antimicrobial functions in acute infections but are now appreciated as functionally versatile cells with critical roles in chronic inflammation. Recent advances in neutrophil biology have contributed to a better understanding of periodontal disease pathogenesis and, reciprocally, the study of periodontitis has led to important insights into neutrophil regulation and function. Here, the contributions by our group to this field through interdisciplinary collaboration are discussed. The study of leukocyte adhesion deficiency‐associated periodontitis has revealed that the connection of neutrophils with destructive inflammation may involve mechanisms beyond the typical bystander injury dogma. In this regard, neutrophils are required for important immunomodulatory functions and their absence from the periodontium leads to dysregulated overproduction of interleukin‐17, which drives inflammatory bone loss. We have also discovered that both the production of neutrophils in the bone marrow and their recruitment to peripheral tissues, including the periodontium, are homeostatically regulated by a secreted protein designated developmental endothelial locus‐1. However, developmental endothelial locus‐1 expression, and hence developmental endothelial locus‐1‐dependent homeostasis, declines considerably with aging and contributes to an increased susceptibility to periodontitis in old age. Moreover, our work has mechanistically supported the concept that periodontitis is a dysbiotic disease and we have shown that neutrophils become targets of immune subversion by periodontal bacteria in a manner that promotes dysbiosis. The mechanism involves microbial exploitation of key neutrophil receptors (complement C5a receptor‐1 and toll‐like receptor‐2), leading to crosstalk signaling that uncouples neutrophil‐mediated killing (which is impaired) from neutrophil‐induced inflammation (which is enhanced). These studies have collectively established new mechanisms governing the protective and destructive functions of neutrophils in periodontitis and offered targeted host‐modulation approaches for the treatment of periodontal diseases.

Neutrophil Extracellular Traps in Periodontitis

“…Different neutrophil defects have been described affecting all stages of neutrophil recruitment and extravasation to periodontal tissue: tethering, rolling, adhesion and endothelial transmigration [23,24]. Most notably, leukocyte adhesion deficiency-I (LAD-I) immunodeficiency, which alters neutrophil extravasation into tissues, presents with periodontitis [25].…”

Relationship between Blood and Standard Biochemistry Levels with Periodontitis in Parkinson’s Disease Patients: Data from the NHANES 2011–2012

“…Despite the homeostasis role of neutrophils in the healthy periodontium [3], they are impaired in periodontitis [1]. The chronic recruitment of excessive neutrophil, and therefore the increase of its serum counts, is learned as a consequence of the persisting microbial dysbiotic challenge [44]. The newness of this study is the likelihood of such parameters presenting predictive value towards periodontitis in PD cases, and future research is warranted to confirm this possibility.…”

“…This result is expected given the infectious nature of periodontitis where bacteria invade the periodontal tissues via the ulcerated epithelium, and leukocytes, in particular neutrophils, are triggered towards the periodontal injury [40][41][42]. Neutrophils had been associated with periodontitis pathogenesis [40,43,44] and were established as key players involved in many inflammatory chronic and aging-related diseases [44]. Neutrophils represent the vast majority (≥95%) of leukocytes recruited to the periodontal pocket [45].…”

Association Between Dietary Inflammatory Index and Periodontitis: A Cross-Sectional and Mediation Analysis

“…On the other hand, PD causes a local inflammatory reaction that can evolve systemically, increasing WBC and segmented neutrophil counts [48,49]. These types of leukocytes are responsible to be in the frontline to fight periodontal infection [50]. If this local infection persists, the bone marrow is signalized to produce a higher number of inflammatory cells [51].…”