Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.
Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD), showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327), also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS) colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.
Department of General Biology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil ; INRA, UMR1319 Micalis, Jouy-en-Josas, France ; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
Clarissa
C
Santos Rocha
Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Ana Cristina
AC
Gomes-Santos
Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Thais
T
Garcias Moreira
Department of General Biology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Marcela
M
de Azevedo
Department of General Biology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Tessalia
T
Diniz Luerce
INRA, Mathématique, Informatique et Génome, UR1077, Jouy-en-Josas, France.
Mahendra
M
Mariadassou
Institute of Biotechnology, Universidade de Caxias do Sul, Caxias do Sul, Brazil.
Ana Paula
AP
Longaray Delamare
INRA, UMR1319 Micalis, Jouy-en-Josas, France ; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
Philippe
P
Langella
INRA, UMR1319 Micalis, Jouy-en-Josas, France ; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
Emmanuelle
E
Maguin
Department of General Biology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Vasco
V
Azevedo
Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Ana Maria
AM
Caetano de Faria
Department of General Biology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Anderson
A
Miyoshi
INRA, UMR1319 Micalis, Jouy-en-Josas, France ; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
Maarten
M
van de Guchte
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D003612:Dairying; D016264:Dextran Sulfate; D005260:Female; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D048668:Lactobacillus delbrueckii / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D016264:Dextran Sulfate