| Differential effects of P-class versus other CpG oligodeoxynucleotide classes on the impaired innate immunity of plasmacytoid dendritic cells in HIV type 1 infection. | |
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MedLine Citation:
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PMID: 20156099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Abstract Human plasmacytoid dendritic cells (PDC) are the major producers of type I interferons (IFN) after stimulation with CpG oligodeoxynucleotides (ODN). HIV-1-infected patients show a deficit in PDC numbers and function with progression of disease. CpG ODN appear to be attractive therapeutics to support the impaired innate immunity in HIV-1 infection. PDC counts, phenotype, and function were analyzed in 23 HIV-infected untreated individuals and 16 controls. Markers for migration (CCR7), activation (CD80), maturation (CD83), and endocytosis (BDCA2) were evaluated at baseline and 20 h after in vitro stimulation with class A, B, C, and P ODN. PDC counts and the expression of BDCA2 on these cells were significantly lower in HIV-1-infected subjects compared to controls (both p < 0.001). After stimulation with CpG ODN, CD80 and CD83 were upregulated to a similar extent in patients and controls, whereas CCR7 was upregulated more efficiently by CpG-P and CpG-C than CpG-A in HIV-1-infected individuals compared to controls. The IFN-alpha induction significantly differed for the CpG ODN classes (A > P > C > B) in patients and controls (p < 0.05). Functional PDC deficits in IFN-alpha and TNF-alpha induction were particularly evident in subjects with less than 500 CD4(+) cells/mul. CpG-P ODNs not only induced remarkable IFN-alpha production in patient PBMCs, but also significantly upregulated the antibacterial and antiviral CXC chemokine IP-10. In conclusion, PDC counts, phenotype, and function are significantly impaired in HIV-1-infected subjects. Optimized P-class ODN may be effective in reversing this innate immune defect, which should be further evaluated in vivo. |
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Authors:
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Norbert Donhauser; Martin Helm; Kathrin Pritschet; Philipp Schuster; Moritz Ries; Klaus Korn; J?rg Vollmer; Barbara Schmidt |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: AIDS research and human retroviruses Volume: 26 ISSN: 1931-8405 ISO Abbreviation: AIDS Res. Hum. Retroviruses Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-16 Completed Date: 2010-04-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709376 Medline TA: AIDS Res Hum Retroviruses Country: United States |
Other Details:
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Languages: eng Pagination: 161-71 Citation Subset: IM; X |
Affiliation:
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German National Reference Centre for Retroviruses, University of Erlangen-N?rnberg , Erlangen, Germany . |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antigens, CD / analysis Antigens, CD80 / analysis Dendritic Cells / chemistry, drug effects*, immunology, virology* HIV Infections / immunology* HIV-1 / immunology* Humans Immunity, Innate* Immunoglobulins / analysis Immunologic Factors / pharmacology* Interferon-alpha / biosynthesis Lectins, C-Type / analysis Male Membrane Glycoproteins / analysis Middle Aged Oligodeoxyribonucleotides / pharmacology* Receptors, CCR7 / analysis Receptors, Immunologic / analysis |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, CD80; 0/CCR7 protein, human; 0/CD83 antigen; 0/CLEC4C protein, human; 0/CPG-oligonucleotide; 0/Immunoglobulins; 0/Immunologic Factors; 0/Interferon-alpha; 0/Lectins, C-Type; 0/Membrane Glycoproteins; 0/Oligodeoxyribonucleotides; 0/Receptors, CCR7; 0/Receptors, Immunologic |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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