Host-microbial interactions in oral mucosa immunopathology

Neutrophils are crucial for oral homeostasis but are also drivers of tissue damage in periodontitis, a common oral immunopathology. The mechanisms determining a protective or detrimental neutrophil response in the periodontium are yet unknown. This project will determine the regulation of neutrophil functions defining periodontal health and diseases.

Oral and peripheral neutrophils will be fully characterized during homeostasis.

A transmigration model will be used to dissect neutrophil adaptation to the periodontal environment, including the acquisition of non-canonical functions.

The impact of gingivitis (self-limiting inflammation) and periodontitis (tissue-damaging) on the phenotypic, transcriptional, and functional profiles of oral and peripheral neutrophils will be assessed. Modulation of helper T cells by neutrophils will also be determined. The ability of neutrophil-related markers in saliva to predict treatment response in periodontitis will be determined.

Neutrophils will be incorporated into an oral mucosa model to assess their response to microbial challenges, induction of tissue damage, and modulation of effector functions.

The periodontal, immunological and molecular characteristics of patients with neutrophil-related primary immunodeficiencies will be determined.

Thorough characterization of neutrophils will reveal insights into disease pathogenesis, new therapeutic targets and markers that may be used to aid in the clinical management of periodontitis.