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

•Epitope Pg14 is anti-atherogenic and Pg19 is proatherogenic in ApoE KO mice.•Pg14 induces regulatory T cells while Pg19 stimulates Th1 cells.•Transcriptional factors Nr4a1 and Nr4a2 are up-regulated by Pg14, but not by Pg19.•BMDC drives regulatory T cells in antigen-nonspecific manner.

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.