Departmental Papers (Dental)
Differential Regulation of Mas-Related G Protein-Coupled Receptor X2- Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas Gingivalis Lipopolysaccharide
Date of this Version
Infection and Immunity
Article number e00246-17
Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690) to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation, but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBLMRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2- mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449 may contribute to the modulation of disease progression. © 2017 American Society for Microbiology.
Antimicrobial peptides; Host response; Lipopolysaccharide; Mast cell; Periodontal immunology; Porphyromonas gingivalis
Gupta, K., Idahosa, C., Roy, S., Lee, D., Subramanian, H., Dhingra, A., Boesze-Battaglia, K., Korostoff, J., & Ali, H. (2017). Differential Regulation of Mas-Related G Protein-Coupled Receptor X2- Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas Gingivalis Lipopolysaccharide. Infection and Immunity, 85 (10), Article number e00246-17-. http://dx.doi.org/10.1128/IAI.00246-17
Date Posted: 08 December 2022
This document has been peer reviewed.