title: Mycobacterium bovis Bacillus Calmette-Guérin killed by extended freeze-drying reduces colitis in mice.
abstract: OBJECTIVE
  Mycobacterium bovis Bacillus Calmette-Guérin (BCG), killed by extended freeze-drying (EFD), induces secretion of interleukin-10 and reduces lung inflammation in a mouse model of asthma. We investigated the effects of EFD BCG in mouse models of inflammatory bowel disease.
  
  
  METHODS
  EFD BCG was administered subcutaneously to mice with colitis induced by dextran sodium sulfate (DSS), oxazolone, or adoptive transfer of CD4(+)CD45RB(high)Foxp3(-) T cells from C57Bl/6 Foxp3GFP mice to RAG2(-/-) mice.
  
  
  RESULTS
  EFD BCG, administered either before induction of DSS and oxazolone colitis or after development of acute or chronic DSS-induced colitis, reduced symptom scores, loss of body weight, and inflammation. Although transfer of CD4(+)CD45RB(high)Foxp3(-) cells induced colitis in RAG2(-/-) mice, administration of EFD BCG at the time of the transfer converted Foxp3(-) T cells to Foxp3(+) T cells and the mice did not develop colitis. EFD BCG protected mice from colitis via a mechanism that required expansion of T regulatory cells and production of interleukin-10 and transforming growth factor β. EFD BCG activated the retinoid X receptor (RXR)-α-peroxisome proliferator-activated receptor (PPAR)-γ heterodimer, blocked translocation of nuclear factor κB to the nucleus, and reduced colonic inflammation; it did not increase the number of colon tumors that formed in mice with chronic DSS-induced colitis.
  
  
  CONCLUSIONS
  EFD BCG controls severe colitis in mice by expanding T regulatory cell populations and PPAR-γ and might be developed to treat patients with inflammatory bowel disease.
authors.affiliation: Institut Pasteur, Laboratoire d'Immunothérapie, Paris, France.
authors.forename: Micheline
authors.initials: M
authors.lastname: Lagranderie
authors.forename: Christoph
authors.initials: C
authors.lastname: Kluge
authors.forename: Helene
authors.initials: H
authors.lastname: Kiefer-Biasizzo
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abolhassani
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Catherine
authors.initials: C
authors.lastname: Fitting
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
authors.forename: Herve
authors.initials: H
authors.lastname: Bercovier
authors.forename: Gilles
authors.initials: G
authors.lastname: Marchal
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005612:Freeze Drying; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis; D016328:NF-kappa B / Q000378:metabolism; D010081:Oxazolone; D047495:PPAR gamma / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss
chemical_list: D001500:BCG Vaccine; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D047495:PPAR gamma; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010081:Oxazolone; D016264:Dextran Sulfate; D009195:Peroxidase