In:
The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 12 ( 2010-06-15), p. 7092-7099
Abstract:
Recent studies have suggested that TLR9 signaling in early endosomes leads to IFN-α production by plasmacytoid dendritic cells (pDCs), whereas TLR9 signaling in late endosomes induces pDC maturation, IL-6, and TNF-α secretion. In this study, we show that human DNA as well as CpG-oligodeoxynucleotides (ODNs) in complex with heat shock protein 90 (Hsp90) stimulate pDCs to produce large quantities of IFN-α. The Hsp90–CpG-A complexes are targeted into the Rab5+, early endosomal Ag 1+-static early endosome postinternalization by DCs, suggesting that preferential sorting of Hsp90-chaperoned self-DNA/CpG-ODNs to the static endosome is required for signaling through TLR9 for IFN-α production. Interestingly, Hsp90-mediated preferential static early endosomal translocation of CpG-ODNs triggers robust IFN-α production from murine conventional DCs. Thus, extracellular Hsp90 converts inert self-DNA/CpG-ODNs into a potent trigger of IFN-α production via spatiotemporal regulation.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1000490
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2010
detail.hit.zdb_id:
1475085-5
detail.hit.zdb_id:
3056-9
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