Modulation of human dendritic cell phenotype and function by probiotic bacteria.
BACKGROUND
"Probiotic" bacteria are effective in treating some inflammatory bowel diseases. However which bacteria confer benefit and mechanisms of action remain poorly defined. Dendritic cells, which are pivotal in early bacterial recognition, tolerance induction, and shaping of T cell responses, may be central in mediating the effects of these bacteria.


OBJECTIVE
To assess effects of different probiotic bacteria on dendritic cell function.


METHODS
Human intestinal lamina propria mononuclear cells, whole blood, or an enriched blood dendritic cell population were cultured with cell wall components of the eight bacterial strains in the probiotic preparation VSL#3 (four lactobacilli, three bifidobacteria, and one streptococcal strains). Dendritic cells were identified and changes in dendritic cell maturation/costimulatory markers and cytokine production in response to probiotic bacteria were analysed by multicolour flow cytometry, in addition to subsequent effects on T cell polarisation.


RESULTS
VSL#3 was a potent inducer of IL-10 by dendritic cells from blood and intestinal tissue, and inhibited generation of Th1 cells. Individual strains within VSL#3 displayed distinct immunomodulatory effects on dendritic cells; the most marked anti-inflammatory effects were produced by bifidobacteria strains which upregulated IL-10 production by dendritic cells, decreased expression of the costimulatory molecule CD80, and decreased interferon-gamma production by T cells. VSL#3 diminished proinflammatory effects of LPS by decreasing LPS induced production of IL-12 while maintaining IL-10 production.


CONCLUSIONS
Probiotic bacteria differ in their immunomodulatory activity and influence polarisation of immune responses at the earliest stage of antigen presentation by dendritic cells.
Antigen Presentation Research Group, Faculty of Medicine Imperial College London, Northwick Park Campus, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
A L
AL
Hart
K
K
Lammers
P
P
Brigidi
B
B
Vitali
F
F
Rizzello
P
P
Gionchetti
M
M
Campieri
M A
MA
Kamm
S C
SC
Knight
A J
AJ
Stagg
D017951:Antigen Presentation; D002454:Cell Differentiation; D002478:Cells, Cultured; D003106:Colon / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology; D010641:Phenotype; D019936:Probiotics / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation
D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma