Synthetic mycoplasma-derived lipopeptide MALP-2 induces maturation and function of dendritic cells.
Dendritic cells (DC) modulate immune responses depending on the nature of the antigens. Receptors capable of discriminating these antigens on the basis of the pathogen-associated molecular patterns (PAMP) belong to the Toll-like receptor (TLR) family. The macrophage-activating lipopeptide 2 kDa (MALP-2), a synthetic lipopeptide derived from Mycoplasma fermentans, signals through TLR-2 and TLR-6. The aim of this study was to examine whether MALP-2 can modulate the functional properties of human monocyte-derived DC. The effects of this treatment were compared to those of the TLR-4 agonist lipopolysaccharide (LPS). To ensure clinical applicability, DC were generated under serum-free conditions. MALP-2 and LPS stimulation induced the expression of CD83 and increased the expressions of CD80, CD86, HLA-ABC and CD40. Furthermore, both substances decreased the endocytotic capacity of DC and induced the release of bioactive TNF-alpha and IL-10, whereas LPS additionally increased IL-12 release. Pretreatment with both substances boosted the allostimulatory capacity of DC. In a coculture with autologous lymphocytes, either MALP-2 or LPS pretreated DC induced a marked proliferation of lymphocytes, but only DC prestimulated with MALP-2 activated lymphocytes to produce the cytokines IL-4, IL-5 and IFN-gamma. No polarisation of lymphocytes into T-helper (Th)1 or Th2 was detected. These data indicate that MALP-2 is a potential candidate to modulate DC for clinical applications.
Weigt
Henning
H
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany. weigt@item.fraunhofer.de
Mühlradt
Peter F
PF
Emmendörffer
Andreas
A
Krug
Norbert
N
Braun
Armin
A
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D004705:Endocytosis; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D009174:Mycoplasma / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018417:Th1 Cells; D018418:Th2 Cells; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D007371:Interferon-gamma; D015847:Interleukin-4; D015848:Interleukin-5; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D000097802:CD83 Antigen; C497964:CD86 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; C106335:macrophage stimulatory lipopeptide 2