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Published on: July 26, 2017
Cathepsins are required for Toll-like receptor 9 responses
Fumi Matsumoto1, Shin-Ichiroh Saitoh, Ryutaroh Fukui
1Division of Infectious Genetics, The Institute of Medical Science, Department of Microbiology and Immunology, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108-8639, Japan.
Biochemical and Biophysical Research Communications
|January 2, 2008
Summary
Cathepsins, lysosomal proteases, are essential for Toll-like receptor 9 (TLR9) DNA recognition. These proteases enable TLR9 to detect microbial DNA within lysosomes, crucial for innate immunity.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Toll-like receptors (TLRs) are key in innate immunity, recognizing microbial products.
- TLR9 specifically detects microbial DNA in lysosomes, but accessory molecules are poorly understood.
- Pathogen sensing by TLR2/4 requires accessory molecules.
Purpose of the Study:
- To identify molecules essential for DNA recognition by Toll-like receptor 9 (TLR9).
- To elucidate the role of lysosomal proteases in TLR9-mediated immune responses.
Main Methods:
- Functional cloning using a Ba/F3 cell line deficient in TLR9 responses.
- Assessing TLR9 responses with cathepsin B/L, S, F, and H.
- Inhibiting cathepsin B/L activity to evaluate its effect on TLR9 responses.
- Investigating the interaction between CpG-B and TLR9 using inhibitors.
Main Results:
- Cathepsins, specifically cathepsin B/L, S, or F, were identified as necessary for TLR9 responses.
- Protease activity of cathepsins was essential for complementing TLR9 function.
- Cathepsin B/L inhibitors reduced TLR9-dependent B cell proliferation and CD86 upregulation.
- Cathepsin B inhibition decreased the interaction between CpG-B and TLR9.
Conclusions:
- Cathepsins play a critical role in the DNA recognition process mediated by TLR9.
- Lysosomal cysteine proteases are required for effective TLR9 signaling and subsequent immune activation.
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