title: Mycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia.
authors: O A
authors: OA
authors: Ovchinnikova
authors: N
authors: N
authors: Berge
authors: C
authors: C
authors: Kang
authors: C
authors: C
authors: Urien
authors: D F J
authors: DF
authors: Ketelhuth
authors: J
authors: J
authors: Pottier
authors: L
authors: L
authors: Drouet
authors: G K
authors: GK
authors: Hansson
authors: G
authors: G
authors: Marchal
authors: M
authors: M
authors: Bäck
authors: I
authors: I
authors: Schwartz-Cornil
authors: M
authors: M
authors: Lagranderie
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000517:prevention & control; D001500:BCG Vaccine / Q000494:pharmacology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005612:Freeze Drying / Q000379:methods; D055633:Immune System Phenomena / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology*; D047495:PPAR gamma / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D047495:PPAR gamma; D016753:Interleukin-10
keywords: EFD BCG; IL-10; atherosclerosis; regulatory T cells