Background & Aims: 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1053/j.gastro.2011.05.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Extended Freeze-Dried BCG Instructed pDCs Induce Suppressive Tregs and Dampen EAE.
Front Immunol
October 2019
Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland.
Several clinical observations have shown that Bacillus Calmette-Guérin (BCG) vaccine has beneficial impact on patients suffering from different chronic inflammatory diseases. Here we evaluated whether BCG inactivated by Extended Freeze-Drying (EFD) which circumvents all the side effects linked to the live bacteria, could influence the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for Multiple Sclerosis. EFD BCG strongly attenuates inflammation, both systemically and at the central nervous system (CNS) level, alleviating EAE.
View Article and Find Full Text PDFThe interplay between bacillus Calmette-Guérin and Treg cells and its role to prevent or cure inflammatory diseases.
Expert Rev Clin Immunol
June 2014
Tolerys, Rue de l'horloge 12, Buchillon 1164, Switzerland.
Clinical evidence indicates that Bacillus Calmette-Guérin (BCG) vaccination exerts anti-inflammatory effects in diseases such as asthma, multiple sclerosis or Type 1 diabetes. Although the exact mechanisms for this activity remain debated, the capacity of mycobacteria to induce regulatory T cells (Tregs) in vivo has been widely reported. However, adverse events associated with live BCG prevent its repeated use, especially in immunocompromised individuals.
View Article and Find Full Text PDFMycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.
J Intern Med
January 2014
Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia.
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.
View Article and Find Full Text PDFHuman leucocytes response to viable, extended freeze-drying or heat-killed Mycobacterium bovis bacillus Calmette-Guérin.
Scand J Immunol
January 2012
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
We investigated the effects of viable, extended freeze-drying (EFD) or heat-killed (HK) Mycobacterium bovis bacillus Calmette-Guérin (BCG) in respiratory burst activity, gene expression of CYBB and NCF1 encoding components of the human phagocyte nicotinamide adenine dinucleotide (NADPH) oxidase, TLR2 expression, and in IL-10 and TNF-α cytokine production by human peripheral blood mononuclear cells (PBMCs). Viable BCG significantly inhibited TLR2 and CYBB gene expression, as well as superoxide release by human PBMC. All BCG stimuli augmented IL-10 release, but only HK BCG or viable BCG increased TNF-α release by PBMCs.
View Article and Find Full Text PDFMycobacterium bovis Bacillus Calmette-Guérin killed by extended freeze-drying reduces colitis in mice.
Gastroenterology
August 2011
Institut Pasteur, Laboratoire d'Immunothérapie, Paris, France.
Background & Aims: 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.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!