Neutrophils Subsets in the Onset of Periodontitis – Su-Per

Widely prevalent, periodontitis is a major public health challenge, causing the irreversible destruction of tooth-supporting tissues. Beyond its local impact, it is closely linked to systemic inflammatory diseases. This condition stems from uncontrolled chronic inflammation driven by oral dysbiosis, often involving Porphyromonas gingivalis. As a result, an overabundance of neutrophils or alterations in their functions may contribute to periodontitis, underscoring the critical need for precise regulation to maintain periodontal homeostasis. P. gingivalis is known to affect neutrophil functions, shifting their role from bactericidal activities and tissue repair to pro-inflammatory and catabolic activity. In this context, we have identified distinct neutrophil subsets interacting with bone cells in experimental models of periodontitis, depending on the presence of P. gingivalis. However, their contribution to disease severity remains poorly understood. We hypothesize that these subsets play distinct roles at different stages of periodontitis, shaping disease progression and tissue damage. Our translational project aims to: 1. Identify neutrophil phenotypes predictive of periodontitis severity in humans, 2. Determine the functions of neutrophil subsets in periodontitis progression, 3. Characterize the crosstalk between neutrophils and P. gingivalis in driving inflammation and bone resorption. This project takes a comprehensive and innovative approach to studying periodontitis, providing a functional analysis of neutrophils involvement using advanced technologies (Deep immune phenotyping using highly multiplexed immunohistology, spectral flow cytometry, and proteomics). It leverages biological collections and experimental models to explore the molecular and cellular mechanisms of periodontitis-associated bone loss. While focused on periodontitis, this novel translational approach allows for a more holistic view of neutrophil behavior, offering new insights into their role in inflammation and bone loss, and serving as a model for developing novel treatment paradigms for neutrophil-driven inflammatory conditions.