Porphyromonas gingivalis HSP60 peptides have distinct roles in the development of atherosclerosis

Different epitope peptides of bacterial heat shock proteins may function as effector or regulatory molecules in autoimmune responses in infection-triggered atherosclerosis. We investigated the mechanisms for the distinct roles of two epitope peptides from Porphyromonas gingivalis heat shock protein 60 (HSP60) in atherogenesis with regard to peptide-specific T cell polarization relevant to (1) phenotype and cytokine profiles, (2) expression of transcription factors, and (3) role of antigen presenting dendritic cell subsets.Apolipoprotein E-knockout (ApoE KO) mice were immunized with peptide 14 or peptide 19 from P. gingivalis HSP60 prior to induction of atherosclerosis by infection with P. gingivalis plus a Western diet. Significant reductions in plaque/lipid droplet area and plasma cholesterol levels were observed in mice immunized with peptide 14, whereas the opposite phenomenon was evident in mice immunized with peptide 19. CD4+ T-cells polarized to the regulatory T-cell type in peptide 14-immunized group, whereas they polarized to the Th1 cells in peptide 19-immunized group; this observation was supported by the cytokine profiles characteristic to each T-cell phenotype.Significantly higher expression of Nr4a1 and Nr4a2 mRNA, transcriptional factors for regulatory T-cell type, were observed in peptide 14-immunized group. In contrast, the expression level of IFN-γ and T-bet mRNA, signaling molecules for Th1 cells, was higher in peptide 19-immunized group than in PBS-immunized group.In non-immunized wild mice, BMDC-derived CD11c+ dendritic cells have shown to stimulate Tregs significantly in antigen-nonspecific manner. However, each peptide antigen demonstrated a unique mode of preferential adoption of dendritic cell subsets.In conclusion, peptide 14 or peptide 19 from P. gingivalis HSP60, respectively, may play either an anti- or pro-atherogenic role in the ApoE KO mouse model of infection-triggered atherosclerosis through distinct mechanisms operating in the polarization of T cells.