Cathepsins are required for Toll-like receptor 9 responses

Journal Article · Fri Mar 14 04:00:00 EDT 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.12.130· OSTI ID:21043661

Matsumoto, Fumi; Saitoh, Shin-ichiroh; Fukui, Ryutaroh ^[1]; Kobayashi, Toshihiko; Tanimura, Natsuko ^[1]; Konno, Kazunori; Kusumoto, Yutaka; Akashi-Takamura, Sachiko ^[1]; Miyake, Kensuke ^[1]

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1. Division of Infectious Genetics, Institute of Medical Science, Department of Microbiology and Immunology, University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108-8639 (Japan)

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 downregulated interaction of CpG-B with TLR9 in 293T cells. These results suggest roles for cathepsins in DNA recognition by TLR9.

• OSTI ID: 21043661
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 367; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CATHEPSINS
CELL PROLIFERATION
CLONING
CYSTEINE
DNA
IMMUNITY
LYSOSOMES
MOLECULES
PATHOGENS
RECEPTORS