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Most Cited Journal Articles 2004-Medical Sciences

Following is a CAS database record representing a highly cited journal article.

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CAS indexed 2 chemical substances from this document. CAS subject entries for this document include: Cell activation; Phosphorothioate oligonucleotides; Transcription factors; and 13 additional concepts.

CAPLUS COPYRIGHT 2005 ACS on STN

TITLE:	A Toll-like receptor recognizes bacterial DNA
AUTHOR(S):	Hemmi, Hiroaki; Takeuchi, Osamu; Kawai, Taro; Kaisho, Tsuneyasu; Sato, Shintaro; Sanjo, Hideki; Matsumoto, Makoto; Hoshino, Katsuaki; Wagner, Hermann; Takeda, Kiyoshi; Akira, Shizuo
CORPORATE SOURCE:	Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and Core Research for Evolutional Science and Technology, Suita, Osaka, 565-0871, Japan
SOURCE:	Nature (London) (2000), 408(6813), 740-745 CODEN: NATUAS; ISSN: 0028-0836
PUBLISHER:	Nature Publishing Group
LANGUAGE:	English

ABSTRACT:
DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinudeotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases. Despite its promising clin. use, the mol. mechanism by which CpG DNA activates immune cells remains unclear. Here the authors show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine prodn. from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.

View the full-text pdf document from the Nature Publishing Group.