Document Detail


Innate Immune Responses in Human Monocyte-Derived Dendritic Cells Are Highly Dependent on the Size and the 5' Phosphorylation of RNA Molecules.
MedLine Citation:
PMID:  21742966     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Recognition of viral genetic material takes place via several different receptor systems, such as retinoic acid-inducible gene I-like receptors and TLRs 3, 7, 8, and 9. At present, systematic comparison of the ability of different types of RNAs to induce innate immune responses in human immune cells has been limited. In this study, we generated bacteriophage 6 and influenza A virus-specific ssRNA and dsRNA molecules ranging from 58 to 2956 nt. In human monocyte-derived dendritic cells (moDCs), short dsRNAs efficiently upregulated the expression of IFN (IFN-α, IFN-β, and IFN-λ1) and proinflammatory (TNF-α, IL-6, IL-12, and CXCL10) cytokine genes. These genes were also induced by ssRNA molecules, but size-specific differences were not as pronounced as with dsRNA molecules. Dephosphorylation of short ssRNA and dsRNA molecules led to a dramatic reduction in their ability to stimulate innate immune responses. Such a difference was not detected for long ssRNAs. RNA-induced cytokine responses correlated well with IFN regulatory factor 3 phosphorylation, suggesting that IFN regulatory factor 3 plays a major role in both ssRNA- and dsRNA-activated responses in human moDCs. We also found that IFN gene expression was efficiently stimulated following recognition of short dsRNAs by retinoic acid-inducible gene I and TLR3 in human embryonic kidney 293 cells, whereas ssRNA-induced responses were less dependent on the size of the RNA molecule. Our data suggest that human moDCs are extremely sensitive in recognizing foreign RNA, and the responses depend on RNA size, form (ssRNA versus dsRNA), and the level of 5' phosphorylation.
Authors:
Miao Jiang; Pamela Osterlund; L Peter Sarin; Minna M Poranen; Dennis H Bamford; Deyin Guo; Ilkka Julkunen
Related Documents :
10023856 - Identification of arthritogenic adjuvants of self and foreign origin.
6245866 - Macrophage factor that induces neutral protease secretion by normal rabbit chondrocytes...
20735866 - Could the expression of cd86 and fcγriib on b cells be functionally related and involv...
21129496 - Macrophages in uveal melanoma and in experimental ocular tumor models: friends or foes?
16036366 - Plasma cytokines and oxidative damage in hiv-positive and hiv-negative adolescents and ...
16007096 - Intracellular protein therapy with socs3 inhibits inflammation and apoptosis.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-8
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  -     ISSN:  1550-6606     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
National Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China;
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Reactive Carbonyls Are a Major Th2-Inducing Damage-Associated Molecular Pattern Generated by Oxidati...
Next Document:  Soluble Proteins Induce Strong CD8+ T Cell and Antibody Responses through Electrostatic Association ...