Document Detail


Interferon-alpha enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing and processing.
MedLine Citation:
PMID:  22184405     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cross-presentation allows antigen-presenting cells to present exogenous antigens to CD8(+) T cells, playing an essential role in controlling infections and tumour development. Interferon-alpha induces the rapid differentiation of human monocytes into dendritic cells, known as IFN-DC, highly efficient in mediating cross-presentation, as well as the cross-priming of CD8(+) T cells. In the present study, we have investigated the mechanisms underlying the cross-presentation ability of IFN-DC, by studying the intracellular sorting of soluble ovalbumin and non structural-3 protein of Hepatitis C virus. Our results demonstrate that, independently from the route and mechanism of antigen entry, IFN-DC are extraordinarily competent in preserving internalised proteins from early degradation and in routing antigens toward the MHC-I processing pathway, allowing long-lasting cross-priming capacity. In IFN-DC both early and recycling endosomes function as key compartments for the storage of both antigens and MHC class-I molecules and for proteasome- and TAP-1-dependent auxiliary cross-presentation pathways. As IFN-DC closely resemble human DC naturally occurring in vivo in response to infections and other danger signals, these findings may have important implications for the design of vaccination strategies in neoplastic or chronic infectious diseases.
Authors:
Francesca Spadaro; Caterina Lapenta; Simona Donati; Laura Abalsamo; Vincenzo Barnaba; Filippo Belardelli; Stefano M Santini; Maria Ferrantini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-19
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Cellular Biology and Neurosciences, Section Experimental Immunotherapy, Istituto Superiore di Sanita, Rome, Italy;
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