Atheroprotective nasal immunization with a heat shock protein 60 peptide from Porphyromonas gingivalis

Abstract

Purpose: Immunization with Porphyromonasgingivalis heat shock protein 60 (PgHSPGO) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSPGO peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. Methods: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSPGO-derived peptide 14 (Pepl4) or peptide 19 (Pepl9), or a Western diet and immunization with Pepl4 or Pepl9 before challenge with Pepl4 or Pepl9. Results: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pepl4 nasal immunization than in mice that received a Western diet and no Pepl4 immunization with or without Pepl4 challenge. An immunoblot profile failed to detect serum reactivity to Pepl4 in any of the study groups. Stimulation by either Pepl4 or Pepl9 strongly promoted the induction of CD4*CD25*forkhead box P3 (FoxP3)* human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4*CD25*FoxP3* Tregs was lower in the Pepl4-immunized mice than in the Pepl4-challenged or Pepl9-immunized mice. Levels of serum interferon gamma (IFN-y) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pepl4-immunized mice than in the other groups. Induction of CD25" IL-17* T helper 17 (Thl7) cells was attenuated in the Pepl4-immunized mice. Conclusions: Nasal immunization with Pepl4 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-y and/or suppressing Thl7-mediated immunity. © 2020. Korean Academy of Periodontology.