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Mycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.

Abstract：

OBJECTIVES:Atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. We have previously shown that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the aim of this study was to investigate the effect of EFD BCG on the development of atherosclerosis. DESIGN:We used two strains of atherosclerosis-prone mice: Ldlr(-/-) (four or six EFD BCG injections) and Apoe(-/-) (six injections). RESULTS:In both models, EFD BCG significantly reduced the size of atherosclerotic lesions, increased IL-10 production and reduced the serum levels of pro-inflammatory cytokines (IL-6, IL-13, KC and tumour necrosis factor-α). Shortly after treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF-κB and increased activity of PPAR-γ in both the spleen and vascular tissue of treated mice. CONCLUSION:EFD BCG has atheroprotective effects through IL-10 production and Treg expansion. These findings support a novel approach to the prevention and treatment of atherosclerosis.

journal_name

J Intern Med

journal_title

Journal of internal medicine

authors

Ovchinnikova OA,Berge N,Kang C,Urien C,Ketelhuth DF,Pottier J,Drouet L,Hansson GK,Marchal G,Bäck M,Schwartz-Cornil I,Lagranderie M

doi

10.1111/joim.12127

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

49-58

issue

1

eissn

0954-6820

issn

1365-2796

journal_volume

275

pub_type

杂志文章

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