Mycobacterial heat shock protein 65 (mbHSP65)-induced atherosclerosis: Preventive oral tolerization and definition of atheroprotective and atherogenic mbHSP65 peptides. Issue 1 (September 2015)

• Record Type: Journal Article
• Authors: Grundtman, Cecilia; Jakic, Bojana; Buszko, Maja; Onestingel, Elisabeth; Almanzar, Giovanni; Demetz, Egon; Dietrich, Hermann; Cappellano, Giuseppe; Wick, Georg
• Is Part Of: Atherosclerosis. Volume 242:Issue 1(2015)
• Page Start: 303
• Page End: 310
• Publication Date: 2015-09
• Subjects: Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.06.044
• Languages: English
• ISSNs: 0021-9150

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Objective</title> <p id="abspara0010">The aim of this study was to identify atherogenic and atheroprotective peptides of bacterial HSP60 [taking mycobacterial HSP65 (mbHSP65) as a potent paradigmatic representative] that could be used as candidates for an orally applied tolerizing vaccine against atherosclerosis.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">ApoE<sup>−/−</sup> mice were immunized with mbHSP65 protein or peptides, given mbHSP65 orally and then kept either on chow or high cholesterol diet. Atherosclerosis was assessed by <italic>en face</italic> and immunohistological analysis. Anti-HSP autoantibodies were detected by ELISA. The number and <italic>in vitro</italic> suppressive function of splenic and lymph node regulatory T cells (Tregs) were analyzed by flow cytometry. Specific T cell reactivity against mbHSP65 protein or peptides was assessed by proliferation assay.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">Decreased lesion size was accompanied by (a) increased splenic Treg numbers; (b) increased interleukin (IL)-10 mRNA levels in the aorta; (c) increased levels of anti-mbHSP65 and anti-mouse HSP60 antibodies pointing to pro-eukaryotic HSP60 humoral crossreaction, not curtailed by oral tolerization; (d) most importantly, we identified and functionally characterized novel atherogenic and atheroprotective mbHSP65 epitopes.</p> </sec> <sec> <title id="sectitle0030">Conclusion</title> <p id="abspara0025">Atheroprotective mbHSP65 peptides may be considered as potential candidates for the development of a tolerizing vaccine to prevent and treat atherosclerosis, while keeping protective immunity to non-atherogenic domains of mbHSP65 intact.</p> </sec> </abstract>