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Mycobacterium bovis Bacillus Calmette-Guérin killed by extended freeze-drying reduces colitis in mice.

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00627235
Contributor : Marie-Christine Vougny <>
Submitted on : Wednesday, September 28, 2011 - 10:50:17 AM
Last modification on : Friday, May 29, 2020 - 3:33:10 PM

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Micheline Lagranderie, Christoph Kluge, Helene Kiefer-Biasizzo, Mohammad Abolhassani, Marie-Anne Nahori, et al.. Mycobacterium bovis Bacillus Calmette-Guérin killed by extended freeze-drying reduces colitis in mice.. Gastroenterology, WB Saunders, 2011, 141 (2), pp.642-52, 652.e1-4. ⟨10.1053/j.gastro.2011.05.002⟩. ⟨pasteur-00627235⟩

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