Induction of high expression of CCR7 and high production of IL-12 in human monocyte-derived dendritic cells by a new bacterial component: LCOS 1013.
Dendritic cells (DCs) are the most potent antigen presenting cells of the immune system as they can act as initiators, stimulators and regulators of the immune response. Human DCs are most commonly generated for clinical use by in vitro differentiation of monocytes with exogenous cytokines. Here, we investigate the effect of LCOS 1013 on the production of mature Mo-DCs. LCOS 1013 is a new bacterial component from walls of gram(+)Klebsellia pneumoniae bacteria that contain some OmpA glycoproteins. Purified peripheral blood monocytes were cultured for 6 days with IL-4 and GM-CSF in order to obtain immature dendritic cells (Im-MoDCs). On day six, Im-MoDCs were matured with either LCOS 1013, TNF alpha, LPS or CD40-Ligand. LCOS 1013 matured Mo-DCs (LCO-DCs) showed a higher expression of DC-LAMP, CD80, CD83, CD54 and CD40 than TNF alpha, LPS and CD40L matured Mo-DCs. Interestingly, LCO-DCs exhibited high expression of full competent CCR7 and high secretion of IL-12 during their maturation. Functionally, LCO-DCs have equivalent potency to trigger mixed leukocyte reaction and antigen-specific reaction and polarize immune response towards Th1 way. Moreover, we found that LCOS 1013 activates DCs through TLR2. LCOS 1013 represents an attractive therapeutic maturation agent of DCs allowing the production of Mo-DCs with high capacity to migrate and to induced Th1 immune responses.
Gillet-Hladky
Stéphanie
S
Immunology Department, Etablissement français du sang, Lyon, France. Immunologie.lyon@efs.sante.fr
Duperrier
Karine
K
Picandet
Stéphanie
S
Mathias
Virginie
V
de Carvalho
Miranda Camila
MC
Bernaud
Janine
J
Masseau
Daniel
D
Bienvenu
Jacques
J
Rigal
Dominique
D
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003713:Dendritic Cells / Q000378:metabolism*; D003911:Dextrans; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006801:Humans; D007202:Indicators and Reagents; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054400:Receptors, CCR7 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003911:Dextrans; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; D054400:Receptors, CCR7; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C015219:fluorescein isothiocyanate dextran; D018664:Interleukin-12; D016650:Fluorescein-5-isothiocyanate