Document Detail


Cross-presenting CD103+ dendritic cells are protected from influenza virus infection.
MedLine Citation:
PMID:  23041628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1-GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103+ DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103+ DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103+ DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway.
Authors:
Julie Helft; Balaji Manicassamy; Pierre Guermonprez; Daigo Hashimoto; Aymeric Silvin; Judith Agudo; Brian D Brown; Mirco Schmolke; Jennifer C Miller; Marylene Leboeuf; Kenneth M Murphy; Adolfo García-Sastre; Miriam Merad
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-01     Completed Date:  2013-01-15     Revised Date:  2014-01-03    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4037-47     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation*
Antigens, CD*
Antigens, Viral / genetics,  immunology
CD8-Positive T-Lymphocytes / immunology*,  pathology
Cell Line
Dendritic Cells / immunology*,  pathology
Dogs
Green Fluorescent Proteins / genetics,  immunology
Influenza A virus / genetics,  immunology*
Integrin alpha Chains*
Interferon Type I / genetics,  immunology
Lung / immunology,  pathology,  virology
Mice
Orthomyxoviridae Infections / genetics,  immunology,  prevention & control*
Receptor, Interferon alpha-beta / genetics,  immunology
Recombinant Fusion Proteins / genetics,  immunology
Signal Transduction / genetics,  immunology
Viral Nonstructural Proteins / genetics,  immunology
Grant Support
ID/Acronym/Agency:
1K99AI095320-01/AI/NIAID NIH HHS; DP2DK083052-01/DK/NIDDK NIH HHS; HHSN266200700010C//PHS HHS; K99 AI095320/AI/NIAID NIH HHS; P01AI058113/AI/NIAID NIH HHS; R01 CA154947/CA/NCI NIH HHS; R01 HL086899/HL/NHLBI NIH HHS; R01AI046954/AI/NIAID NIH HHS; U01 AI095611/AI/NIAID NIH HHS; U01 AI10008/AI/NIAID NIH HHS; U19AI083025/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Viral; 0/INS1 protein, influenza virus; 0/Integrin alpha Chains; 0/Interferon Type I; 0/Recombinant Fusion Proteins; 0/Viral Nonstructural Proteins; 0/alpha E integrins; 147336-22-9/Green Fluorescent Proteins; 156986-95-7/Receptor, Interferon alpha-beta
Comments/Corrections

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