PolyI:C-induced reduction in uptake of soluble antigen is independent of dendritic cell activation.
Dendritic cells (DC) are key players in the initiation and modulation of adaptive immune responses due to their ability to acquire and present antigen and stimulate T cells. For the induction of effector T cell functions, antigen must be presented by activated DC. In this study, we have compared uptake of antigen by mouse DC in the presence of different Toll-like receptor (TLR) agonists, which are potent inducers of DC activation. Here we show that the reduction in uptake of soluble antigen in the presence of the viral double-stranded RNA (dsRNA) analogues polyinosinic-polycytidylic acid and Ampligen is independent of TLR-mediated DC activation. A reduction in antigen uptake by bone marrow-derived and splenic DC was also observed in response to other RNA homopolymers such as polyinosinic and polyguanylic acids, which are known inhibitors of scavenger receptor-mediated endocytosis. Pinocytosis and mannose receptor-mediated uptake of soluble antigen were not affected by any of the tested nucleic acids. The reduction in antigen uptake by dsRNA did not negatively influence the T cell stimulating properties of the DC. In summary, we conclude that the decrease in antigen endocytosis observed in the presence of a variety of TLR agonists is independent of TLR signalling and is caused by competition for specific surface receptors that are involved in the uptake of these TLR agonists and the antigen.
Tirapu
Iñigo
I
Peter Gorer Department of Immunobiology, King's College London, Guy's Hospital, London, UK.
Giquel
Benoit
B
Alexopoulou
Lena
L
Uematsu
Satoshi
S
Flavell
Richard
R
Akira
Shizuo
S
Diebold
Sandra S
SS
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D007369:Interferon Inducers / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010873:Pinocytosis / Q000187:drug effects / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; C408982:CPG-oligonucleotide; D007369:Interferon Inducers; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009838:Oligodeoxyribonucleotides; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D011070:Poly I-C