Bacterial metabolite interference with maturation of human monocyte-derived dendritic cells.
Dendritic cells (DC), the most potent APC, are central to antimicrobial immunity. Because of evolutionary pressure, it is reasonable that pathogens have evolved strategies to also subvert this host-defense mechanism. In the present study, we describe a novel way of bacterial interference with DC maturation. The bacterial metabolite n-butyrate, which occurs physiologically in high concentrations in the gastrointestinal tract and has well-known anti-inflammatory effects, is able to prevent LPS-induced maturation of DC resulting in a reduced capability to stimulate T cells. In particular, n-butyrate prevents homotypic DC clustering, inhibits IL-12 while sparing IL-10 production, and at the molecular level, blocks NF-kappa B translocation. These results demonstrate efficient targeting of DC function by a bacterial metabolite, which might explain the particular type of immune responsiveness in the presence of this bacterial agent as exemplified in the gastrointestinal tract.
Säemann
Marcus D
MD
Institute of Immunology, University of Vienna, Austria.
Parolini
Ornella
O
Böhmig
Georg A
GA
Kelemen
Peter
P
Krieger
Peter-Michael
PM
Neumüller
Josef
J
Knarr
Katharina
K
Kammlander
Willibald
W
Hörl
Walter H
WH
Diakos
Christos
C
Stuhlmeier
Karl
K
Zlabinger
Gerhard J
GJ
D000328:Adult; D001419:Bacteria / Q000276:immunology* / Q000378:metabolism; D002087:Butyrates / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007109:Immunity; D009000:Monocytes / Q000166:cytology / Q000276:immunology
D002087:Butyrates