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International Immunology Advance Access originally published online on June 7, 2009
International Immunology 2009 21(7):871-879; doi:10.1093/intimm/dxp053
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© The Author 2009. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

PolyI:C-induced reduction in uptake of soluble antigen is independent of dendritic cell activation

Iñigo Tirapu1, Benoit Giquel1, Lena Alexopoulou2, Satoshi Uematsu3, Richard Flavell4, Shizuo Akira3,5 and Sandra S. Diebold1

1 Peter Gorer Department of Immunobiology, King's College London, Guy's Hospital, London SE1 9RT, UK
2 Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Parc Scientifique de Luminy, Case 906, 13288 Marseille, France
3 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita city, Osaka 565-0871, Japan
4 Department of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, CT, USA
5 Solution-oriented research for Science and Technology, Japan Science and Technology Corporation, Osaka 565-0871, Japan

Correspondence to: S. Diebold; E-mail: sandra.diebold{at}kcl.ac.uk

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.

Keywords: antigen uptake, dendritic cells, endocytosis, Toll-like receptors

Transmitting editor: A. Cooke

Received 15 December 2008, accepted 12 May 2009.


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