Capture of cell-derived microvesicles (exosomes and apoptotic bodies) by human plasmacytoid dendritic cells

Abstract

cDCs and pDCs differ in multiple aspects. Among those, antigen capture is a recognized feature of cDCs, whereas pDCs display poor capacity to capture cell-derived antigens. However, animal models of organ transplantation suggested a role for pDCs in tolerance induction via phagocytosis of donor antigens. In a transplantation setting, microvesicles, such as apoptotic bodies and exosomes secreted by the graft, may be potential sources of alloantigen. Here, we tested the capacity of human pDCs to capture exosomes and apoptotic bodies from Jurkat T cells. Exosomes and apoptotic bodies were indeed captured by pDCs, although required longer times of incubation when compared with the highly endocytic cDCs. In cDCs and pDCs, exosome capture was more efficient than apoptotic bodies. Endocytosis inhibitors clearly impaired exosome capture by cDCs, although this could not be verified in pDCs as a result of cellular toxicity. Functionally, capture of Jurkat-derived exosomes did not induce nor prevent pDC maturation, and exosome-loaded pDCs induced T cell proliferation, suggesting a link between capture and presentation. Thus, exosomes and apoptotic bodies may be sources of antigen for human pDCs.

Plasmacytoid dendritic cells of the gut: Relevance to immunity and pathology

“…So how close are pDCs to cDCs in this capacity? Bastos-Amador et al recently reported that human pDCs have the ability to capture and present exosomes and apoptotic bodies from Jurkat T cells [70]. These observations are consistent with previous reports that identify pDCs as phagocytic antigen-presenting cells essential for tolerance to vascularized cardiac allografts in an animal model of organ transplantation [71].…”

Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections

“…It is likely that, in vivo , pDC recognize and engulf apoptotic bodies or exosomes released by MCMV-infected cells, (Figure 2B, ❶), as was demonstrated for other viruses (Dreux et al, 2012) or tumor cells (Bastos-Amador et al, 2012). pDC could also directly recognize and engulf viral particles (Figure 2B, ❷).…”

Plasmacytoid Dendritic Cells Respond Directly to Apoptotic Cells by Secreting Immune Regulatory IL-10 or IFN-α

“…They have been shown to lessen the severity of autoimmune mediated arthritis and asthma in mice (48, 49). Human pDCs can also ingest microvesicles from apoptotic cells and present the antigen to T cells (50). In the presence of apoptotic cells, TLR7 activated pDCs greatly augmented T cell expression of IL-10, without affecting T cell proliferation.…”