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Toll‐like receptor (TLR) 3 immune modulation by unformulated small interfering RNA or DNA and the role of CD14 (in TLR‐mediated effects)
Author(s) -
Weber Cordula,
Müller Christian,
Podszuweit Anja,
Montino Carmen,
Vollmer Jörg,
Forsbach Alexandra
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2012.03559.x
Subject(s) - tlr3 , tlr7 , nucleic acid , innate immune system , small interfering rna , biology , toll like receptor , rna , tlr9 , cd14 , microbiology and biotechnology , immune system , receptor , pattern recognition receptor , rna interference , rna silencing , dna , biochemistry , gene , gene expression , immunology , dna methylation
Summary The Toll‐like receptors (TLRs) 3, 7, 8 and 9 stimulate innate immune responses upon recognizing pathogen‐derived nucleic acids. TLR3 is located on the cell surface and in cellular endosomes and recognizes double‐stranded viral RNA or the synthetic mimic poly rI:rC. Recently, unformulated small interfering RNA (siRNA) has been reported as ligand for surface‐expressed murine TLR3. Blockage of TLR3 is achieved by single‐stranded DNA. We confirm and expand the observation that poly rI:rC‐mediated TLR3 immune activation is blocked in a sequence‐, length‐, backbone‐ and CpG‐dependent manner. However, human TLR3 is not activated by siRNA, which may be the result of differences in the amino acid composition of the TLR3 loop 1 of mice and humans. Although CD14 was previously described as a co‐receptor for murine TLR3 and other nucleic acid‐recognizing TLRs, human CD14 acts only as co‐receptor to human TLR9, but not TLR3, TLR7 or TLR8. We show that CD14 up‐regulates the TLR9 immune response of A, B and C‐class oligodeoxynucleotides but down‐regulates the phosphoro‐diester version of B‐class oligodeoxynucleotides.