Research progress on macrophage polarization, pyroptosis, and efferocytosis in periodontitis

The irreversible destruction of periodontal tissue caused by periodontitis is the result of an imbalance between external pathogenic factors and the internal immune response. As human immune cells, macrophages have both pro- and anti-inflammatory roles in the occurrence and development of periodontitis. Pathogenic bacteria, inflammatory cytokines, and neutrophils in the periodontal microenvironment can significantly affect the metabolism and functional status of macrophages, and the status of macrophages can regulate disease processes. By activating the NF-κB signaling pathway, the bacteria cause macrophages to undergo M1 proinflammatory polarization and pyroptosis, forming a microenvironment that induces periodontal tissue destruction. With the development of the disease, numerous apoptotic neutrophils are recognized and phagocytized by macrophages (i.e. efferocytosis), which can both inhibit the NF-κB pathway and activate the nuclear receptors PPAR and LXR, promoting the anti-inflammatory polarization of M2 and further enhancing the efferocytosis activity of macrophages. As a result, these treatments can limit tissue inflammatory damage and promote tissue repair. In recent years, periodontitis treatment strategies focusing on macrophage regulation have received extensive attention, including gene knockout, nanoparticles, exosomes, miRNA, and polyunsaturated fatty acid diets. In this article, we review the specific role of macrophages in periodontitis from three aspects, including macrophage polarization, pyroptosis, and efferocytosis, which may improve our understanding of periodontitis and provide possible directions for periodontitis treatment strategies.