Targeted delivery of CpG ODN to CD32 on human and monkey plasmacytoid dendritic cells augments IFNα secretion

Immunobiology
Jurjen TelI Jolanda M de Vries

Abstract

Atopic diseases are characterized by the presence of Th2 cells. Recent studies, in mice and man, demonstrated that allergen-specific Th2 responses can be shifted to Th0/Th1 responses. Plasmacytoid dendritic cells (pDCs) produce large amounts of type I interferons (IFNs) after stimulation of Toll Like Receptor 9 (TLR9) and are likely to play an important role in the reorientation of these Th2 cells. The expression of CD32a on the cell surface of pDCs makes this cell type attractive for targeted delivery of antigen and TLR agonists to revert Th2 responses. Therefore we sought to determine the efficacy of targeted delivery of CpG-C ODN to CD32a on the ability of human and monkey pDCs to secrete inflammatory cytokines. Here we demonstrate that targeted delivery of 3'-biotinylated CpG-C to CD32a on pDC induced phenotypical maturation as determined by CD80, CD83 and CD86 expression. Furthermore, targeting both monkey and human pDCs strongly augmented the secretion of IFNα compared to the delivery of CpG-C in an untargeted fashion (p<0.001). TLR9 induced activation hampers the ability of human pDCs to internalize CD32a. Therefore we opted for targeted delivery of CpG-ODNs to CD32a, which reduces the risk of undesired side effects of s...Continue Reading

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Mar 18, 2011·European Journal of Immunology·Jurjen TelI Jolanda M de Vries

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Citations

Jan 22, 2014·Nature Reviews. Immunology·Martin GuilliamsBart N Lambrecht
May 15, 2012·Biochimica Et Biophysica Acta·Giuseppe PalmaClaudio Arra
Mar 12, 2015·Frontiers in Immunology·Lisa T C VogelpoelJeroen den Dunnen
Aug 30, 2018·Human Vaccines & Immunotherapeutics·J A Sepulveda-ToepferGeert Cornelius Mudde
Oct 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jurjen TelI Jolanda M de Vries

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