Objective: This study aimed to study the roles of Muramyl Dipeptide (MDP) which is an agonist of NOD2 in Dendritic Cells (DCs) exposed to Porphyromonas gingivalis lipopolysaccharide (P. gingivalis- LPS) on maturation and antigen-presenting functions of DCs to provide experimental evidences to explore the possible mechanism of DCs in periodontitis.
Methods: Flow cytometry was used to detect CD11c, MHC-II, CD80, CD86, and CD40 expression on DCs and ELISA was used to detect IL-12, IFN-γ, IL-10, and IL-13 secreted by DCs which were stimulated by MDP and P. gingivalis-LPS, respectively or in synergism. RT-PCR analysis was used to detect NOD2, TLR2, and TLR4 mRNA expression in DCs stimulated by MDP and P. gingivalis-LPS, respectively or in synergism. CCK8 was used to assess CD4+ T cells proliferation after co-cultured with DCs stimulated by MDP and P. gingivalis-LPS, respectively or in synergism and ELISA was used to detect IL-2, IFN-γ, IL-10 and IL-13 secreted by these T cells.
Results: MDP had weak ability to stimulate DCs maturation but MDP could promote DCs maturation stimulated by P. gingivalis-LPS. MDP was NOD2 agonist to DCs and P. gingivalis- LPS was TLR2 but not TLR4 agonist to DCs. MDP could facilitate TLR2 mRNA expression in DCs exposed to P. gingivalis- LPS. The ability of MDP to promote DCs secreting cytokines was far below P. gingivalis-LPS but MDP could promote the functions of Th2 cell-promoting DCs induced by P. gingivalis-LPS. MDP could promote CD4+T cells proliferation primed by DCs exposed to P. gingivalis-LPS and elevate the ability of DCs exposed to P. gingivalis-LPS to prime Th0 cells to Th2 cells.
Conclusion: Intracellular NOD2 in DCs could be activated by MDP and this activation could promote maturation and the ability to prime Th0 cells to Th2 cells of DCs exposed to P. gingivalis-LPS.Author(s): Han Su, Xiang Yan, Wei Chen, Ting Guo, Zi-Tong Lin, Qin-Gang Hu