Filifactor alocis Disrupts Efferocytosis to Sustain Inflammation in Periodontitis

Authors

Ella Dye, University of LouisvilleFollow
Silvia Uriarte, University of LouisvilleFollow
Ruth Idowu, University of LouisvilleFollow

Program/Event

Arts and Research Showcase 2025

Abstract

Background: Filifactor alocis is a Gram-positive, obligate anaerobe that has emerged as a diagnostic marker of periodontitis. Neutrophils and macrophages are key players in oral immune homeostasis. Neutrophils are short-lived cells and constitutively undergo apoptosis. This apoptotic program can be accelerated or delayed by bacterial interactions. Macrophages clear apoptotic neutrophils via “efferocytosis,” a crucial mechanism for resolving inflammation and preventing tissue damage. The efferocytic process downregulates the expression and release of proinflammatory cytokines such as interleukin (IL)-6 and IL-23 while promoting anti-inflammatory responses. Our previous findings demonstrated that F. alocis delays neutrophil apoptosis, with fewer apoptotic cells observed after 18 hours of bacterial stimulation. Despite this, our preliminary data showed that human monocyte-derived macrophages (HMDMs) engulf F. alocis-infected neutrophils at levels comparable to uninfected apoptotic neutrophils. However, whether this interaction promotes inflammation remains unclear. We hypothesized that macrophages' engulfment of F. alocis-infected neutrophils induces proinflammatory cytokine release, contributing to dysregulated inflammation in periodontitis.

Methods: Human neutrophils were stimulated with or without F. alocis for 18 hours. Afterward, neutrophils were co-incubated with HMDMs for 2 hours and subsequently stimulated with lipopolysaccharide (LPS) overnight. IL-6 and IL-23 mRNA expression levels were quantified using qPCR.

Results: The macrophages’ engulfment of F. alocis-infected neutrophils significantly increased IL-6 and IL-23 mRNA expression upon LPS stimulation, suggesting sustained inflammation. As expected, macrophage engulfment of apoptotic neutrophils reduced IL-6 and IL-23 mRNA expression, supporting an anti-inflammatory phenotype.

Conclusions: Efferocytosis of apoptotic neutrophils promotes inflammation resolution, whereas the engulfment of F. alocis-infected neutrophils triggers a proinflammatory response, sustaining inflammation. These findings suggest a novel immune evasion strategy by which F. alocis disrupts neutrophil-macrophage interactions, contributing to periodontitis pathogenesis.

Recommended Citation

Dye, Ella; Uriarte, Silvia; and Idowu, Ruth (2025) "Filifactor alocis Disrupts Efferocytosis to Sustain Inflammation in Periodontitis," The Cardinal Edge: Vol. 3: Iss. 2, Article 25.
Available at: https://ir.library.louisville.edu/tce/vol3/iss2/25