Targeting uptake receptors on human plasmacytoid dendritic cells triggers antigen cross-presentation and robust type I IFN secretion.
J Immunol
; 191(10): 5005-12, 2013 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-24127556
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Interferon Tipo I
/
Apresentação de Antígeno
/
Apresentação Cruzada
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Holanda