Cathepsins are required for toll-like receptor 9 responses

被引：130

作者：

Matsumoto, Fumi ^{[1
]}

Saitoh, Shin-ichiroh ^{[1
]}

Fukui, Ryutaroh ^{[1
]}

Kobayashi, Toshihiko ^{[1
,2
]}

Tammura, Natsuko ^{[1
,2
]}

Konnio, Kazunori ^{[1
]}

Kusumoto, Yutaka ^{[1
]}

Akashi-Takamura, Sachiko ^{[1
]}

Miyake, Kensuke ^{[1
]}

机构：

[1] Univ Tokyo, Dept Microbiol & Immunol, Inst Med Sci, Div Infect Dis,Minatoku, Tokyo 1088639, Japan

[2] Japan Soc Promot Sci, Tokyo 1028472, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 367卷 / 03期

关键词：

toll-like receptor; innate immunity; protease;

D O I：

10.1016/j.bbrc.2007.12.130

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Toll-like receptors (TLR) recognize a variety of microbial products and activate defense responses. Pathogen sensing by TLR2/4 requires accessory molecules, whereas little is known about a molecule required for DNA recognition by TLR9. After endocytosis of microbes, microbial DNA is exposed and recognized by TLR9 in lysosomes. We here show that cathepsins, lysosomal cysteine proteases, are required for TLR9 responses. A cell line Ba/F3 was found to be defective in TLR9 responses despite enforced TLR9 expression. Functional cloning with Ba/F3 identified cathepsin B/L as a molecule required for TLR9 responses. The protease activity was essential for the complementing effect. TLR9 responses were also conferred by cathepsin S or F, but not by cathepsin H. TLR9-dependent B cell proliferation and CD86 upregulation were apparently downregulated by cathepsin B/L inhibitors. Cathepsin B inhibitor clownregulated interaction of CpG-B with TLR9 in 293T cells. These results suggest roles for cathepsins in DNA recognition by TLR9. (c) 2007 Elsevier Inc. All rights reserved.

引用

收藏

页码：693 / 699

页数：7

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