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J Intern Med. 2014 Jan;275(1):49-58. doi: 10.1111/joim.12127. Epub 2013 Sep 12.

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

Author information

1
Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia.

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.

KEYWORDS:

EFD BCG; IL-10; atherosclerosis; regulatory T cells

PMID:
23962000
DOI:
10.1111/joim.12127
[Indexed for MEDLINE]
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