Supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells.
BACKGROUND
Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn) could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK), glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K) pathways on biological functions of human monocyte-derived DCs treated with BbC50sn.


RESULTS
DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS) or Zymosan, with or without specific inhibitors of p38MAPK (SB203580), ERK (PD98059), PI3K (LY294002) and GSK3 (SB216763). We found that 1) the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2) p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3) ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4) BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS.


CONCLUSIONS
We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria.
Hoarau
Cyrille
C
UPRES EA 4245 Cellules Dendritiques & Greffes, Université François-Rabelais, Tours, France. cdg@med.univ-tours.fr
Martin
Laurence
L
Faugaret
Delphine
D
Baron
Christophe
C
Dauba
Audrey
A
Aubert-Jacquin
Cécile
C
Velge-Roussel
Florence
F
Lebranchu
Yvon
Y
D001644:Bifidobacterium / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000382:microbiology; D005285:Fermentation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity; D007107:Immune System; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D038362:Glycogen Synthase Kinase 3