Work

Macrophage functional plasticity in periodontitis: microenvironmental regulation, disease progression, and therapeutic targeting

Year: 2026

Type: review

Abstract: Periodontitis is a chronic inflammatory disease driven by periodontal microbial dysbiosis and dysregulated host immune responses. Its progression is characterized by persistent inflammation, destruction of periodontal soft tissues, disrupted alveolar bone remodeling, and impaired tissue repair. As key effector cells within the periodontal immune microenvironment, macrophages contribute to pathogen clearance, inflammatory regulation, bone homeostasis, and tissue repair. Macrophage responses are highly heterogeneous and context dependent, extending well beyond the conventional M1/M2 dichotomy. This review focuses on macrophage functional plasticity in periodontitis, defined here as context-dependent changes in macrophage functional responses rather than heterogeneity or state-associated signatures alone, and examines how periodontal microorganisms and their virulence factors, host inflammatory signals, hypoxia and oxidative stress, immunometabolic changes, and epigenetic and post-transcriptional mechanisms regulate these responses. We further discuss how these responses contribute to inflammatory amplification, extracellular matrix degradation, alveolar bone resorption, resolution of inflammation, and periodontal tissue repair. Emerging evidence indicates that macrophage dysregulation in periodontitis extends beyond an imbalance between pro-inflammatory and repair-associated functions to include alterations in macrophage subset composition and selected functional programs. Direct evidence tracking transitions within macrophage populations in periodontal lesions, however, remains limited. The strategies reviewed here target inflammatory pathways, immunometabolism, intercellular communication, and the local tissue microenvironment. Linking changes in macrophage function to tissue outcomes may clarify the immunopathogenesis of periodontitis and inform treatments that promote inflammation resolution and periodontal regeneration.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1973755

Authors: Ziqi Gu, Xinyu Li, Gulinur Awuti

Institutions: First Affiliated Hospital of Xinjiang Medical University, Chengdu University of Traditional Chinese Medicine

Language: English

Topic: Oral microbiology and periodontitis research

Subfield: Periodontics

Field: Dentistry

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801