Periodontitis,a prevalent microbe-driven disease,is characterized by the progressive destruction of tooth-supporting tissues.Porphyromonas gingivalis(P.gingivalis),a keystone pathogen in chronic periodonti-tis,evades ...Periodontitis,a prevalent microbe-driven disease,is characterized by the progressive destruction of tooth-supporting tissues.Porphyromonas gingivalis(P.gingivalis),a keystone pathogen in chronic periodonti-tis,evades clearance by periodontal immune cells,leading to microbial dysbiosis and alveolar bone re-sorption.Effective treatment requires the elimination of periodontopathogens and restoration of alveolar bone.Macrophages serve as the primary defense against periodontal pathogens.Cell stiffness,an intrin-sic mechanical property of macrophage,is closely linked to their motility,deformability,and phagocytic function,presenting a potential target for enhancing macrophage antibacterial activities.Black phospho-rus nanosheets(BPNS),a novel two-dimensional material that degrades into nontoxic phosphate in phys-iological environments,offer distinct advantages in bone regeneration.In this study,BPNS was functional-ized with spermidine(Spd),a natural polyamine with immunomodulatory effects,to improve periodon-tal infection control.In addition to preserving BPNS's osteogenic activity,BPNS@Spd further enhanced macrophage antibacterial function by targeting cell stiffness.Reduced cell stiffness enhanced macrophage deformability and membrane fluidity,facilitating more efficient phagocytosis and clearance of P.gingi-valis.Mechanistically,BPNS@Spd modulated macrophage stiffness and function by decreasing membrane cholesterol content,in which autophagy-mediated cholesterol efflux plays a critical role.This work under-scores the potential of modulating membrane cholesterol and cell stiffness to boost macrophage-mediated bacterial clearance,offering an innovative immunomodulatory approach for managing microbe-driven in-flammatory diseases beyond periodontitis.展开更多
基金supported by the National Key Re-search and Development Program of China(No.2023YFB3809904)the National Natural Science Foundation of China(Nos.82373255 and 82001005)+2 种基金the Natural Science Foundation of Guangdong Province,China(Nos.2024A1515012918 and 2023A1515030015)the Special Funds for the Cultivation of Guangdong College Stu-dents’Scientific and Technological Innovation(“Climbing Program”Special Funds.pdjh2024b018)the National Undergraduate Train-ing Program for Innovation and Entrepreneurship(No.20240543).
文摘Periodontitis,a prevalent microbe-driven disease,is characterized by the progressive destruction of tooth-supporting tissues.Porphyromonas gingivalis(P.gingivalis),a keystone pathogen in chronic periodonti-tis,evades clearance by periodontal immune cells,leading to microbial dysbiosis and alveolar bone re-sorption.Effective treatment requires the elimination of periodontopathogens and restoration of alveolar bone.Macrophages serve as the primary defense against periodontal pathogens.Cell stiffness,an intrin-sic mechanical property of macrophage,is closely linked to their motility,deformability,and phagocytic function,presenting a potential target for enhancing macrophage antibacterial activities.Black phospho-rus nanosheets(BPNS),a novel two-dimensional material that degrades into nontoxic phosphate in phys-iological environments,offer distinct advantages in bone regeneration.In this study,BPNS was functional-ized with spermidine(Spd),a natural polyamine with immunomodulatory effects,to improve periodon-tal infection control.In addition to preserving BPNS's osteogenic activity,BPNS@Spd further enhanced macrophage antibacterial function by targeting cell stiffness.Reduced cell stiffness enhanced macrophage deformability and membrane fluidity,facilitating more efficient phagocytosis and clearance of P.gingi-valis.Mechanistically,BPNS@Spd modulated macrophage stiffness and function by decreasing membrane cholesterol content,in which autophagy-mediated cholesterol efflux plays a critical role.This work under-scores the potential of modulating membrane cholesterol and cell stiffness to boost macrophage-mediated bacterial clearance,offering an innovative immunomodulatory approach for managing microbe-driven in-flammatory diseases beyond periodontitis.
