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Targeting uptake receptors on human plasmacytoid dendritic cells triggers antigen cross-presentation and robust type I IFN secretion. | LitMetric

AI Article Synopsis

  • Plasmacytoid dendritic cells (pDCs) are essential for starting immune responses by producing type I interferons, and their role in presenting antigens is being reassessed.
  • The study investigates which receptors on pDCs can best take up and present antigens, finding that targeting specific receptors with nanoparticles allows for effective antigen processing and presentation to T cells.
  • The research highlights that pDCs not only present antigens effectively but also produce important cytokines when activated, suggesting they could be leveraged in cancer immunotherapy strategies.

Article Abstract

Plasmacytoid dendritic cells (pDCs) play a crucial role in initiating immune responses by secreting large amounts of type I IFNs. Currently, the role for human pDCs as professional APCs in the cross-presentation of exogenous Ags is being re-evaluated. Human pDCs are equipped with a broad repertoire of Ag uptake receptors and an efficient Ag-processing machinery. In this study, we set out to investigate which receptor can best be deployed to deliver Ag to pDCs for Ag (cross-)presentation. We show that targeting nanoparticles to pDCs via the C-type lectins DEC-205, DC immunoreceptor, blood DC Ag-2, or the FcR CD32 led to uptake, processing, and (cross-) presentation of encapsulated Ag to both CD4(+) and CD8(+) T cells. This makes these receptors good candidates for potential in vivo targeting of pDCs by nanocarriers. Notably, the coencapsulated TLR7 agonist R848 efficiently activated pDCs, resulting in phenotypical maturation as well as robust IFN-α and TNF-α production. Taken together, their cross-presentation capacity and type I IFN production to further activate components of both the innate and adaptive immune system mark pDCs as inducers of potent antitumor responses. These findings pave the way to actively recruit human pDCs for cellular cancer immunotherapy.

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Source
http://dx.doi.org/10.4049/jimmunol.1300787DOI Listing

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