Abstract:
:Toll-like receptors (TLR) 7 and 8 are closely related members of the TLR family of pathogen-associated molecular pattern recognition receptors and have an important function in activation of innate immune responses upon viral infection. TLR7 can be activated selectively by the guanosine analogue loxoribine, whereas the imidazoquinoline derivative Resiquimod (R-848) activates both TLR7 and TLR8. We demonstrate that co-incubation of R-848 with thymidine homopolymer oligodeoxynucleotides (ODN) significantly increased activity of R-848 on TLR8-expressing HEK 293 cells, but abolished TLR7-mediated signaling. Similarly, the combination of loxoribine and thymidine ODN redirected the stimulatory effect of loxoribine away from TLR7, and toward TLR8. This alteration in ligand specificity was demonstrated both in TLR-transfected HEK cells, and also in human PBMC, with a corresponding change in cytokine production away from IFN-alpha secretion by TLR7-expressing plasmacytoid DC and toward IL-12, TNF-alpha and IFN-gamma secretion by TLR8-expressing monocytes and NK cells. These results demonstrate an unexpected plasticity in the ligand specificities of TLR7 and TLR8, and suggest a novel sequence-selective interaction between these receptors and synthetic phosphorothioate ODN.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Jurk M,Kritzler A,Schulte B,Tluk S,Schetter C,Krieg AM,Vollmer Jdoi
10.1002/eji.200535806subject
Has Abstractpub_date
2006-07-01 00:00:00pages
1815-26issue
7eissn
0014-2980issn
1521-4141journal_volume
36pub_type
杂志文章abstract::In man, B cell maturation factors obtained from T cells or T cell lines have been shown to induce antibody formation in mitogen or anti-immunoglobulin activated B cells, and in some continuous B cell lines, but the relationships between these factors and B cell differentiation factors in antigen-specific antibody resp...
journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830210633
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240205
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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