Kyrklund M, Kummu O, Kankaanpää J, Akhi R, Nissinen A, Turunen SP, et al. (2018) Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein. PLoS ONE 13(1): e0191216. https://doi.org/10.1371/journal.pone.0191216
Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein
|Author:||Kyrklund, Mikael1,2; Kummu, Outi1,2; Kankaanpää, Jari1,2;|
1Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu
2Medical Research Center and Nordlab Oulu, University Hospital and University of Oulu
3Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital
|Online Access:||PDF Full Text (PDF, 5.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201803276216
Public Library of Science,
|Publish Date:|| 2018-03-28
Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression of atherosclerosis. We aimed to investigate whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL) and how it would affect the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share cross-reactive epitopes that prompt IgM antibody production and consequently confer atheroprotection. A significant negative association was observed between atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice, supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA levels to Rgp44 and toPg in both Rgp44- and Pg-immunized mice were significantly higher than those in saline control, suggesting that IgA to Rgp44 could be a surrogate marker of immunization in Pg-immunized mice. Distinct antibody responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS), and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations, indicating that different immunogenic components between Rpg44 and Pg may behave differently in regard of their roles in the development of atherosclerosis. Immunization with Rgp44 also displayed atheroprotective features in modulation of plaque size through association with plasma levels of IL-1α whereas whole Pg bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5 and IL-10. The present study may contribute to refining therapeutic approaches aiming to modulate immune responses and inflammatory/anti-inflammatory processes in atherosclerosis.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
This study was funded by Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research. Sigrid Juselius Foundation webpage: http://sigridjuselius.fi/sv/ Finnish Foundation for Cardiovascular Research (Sydäntutkimussäätiö) webpage: http://www.sydantutkimussaatio.fi/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2018 Kyrklund et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.