Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9
SCIE
SCOPUS
- Title
- Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9
- Authors
- Park, B; Brinkmann, MM; Spooner, E; Lee, CC; Kim, YM; Ploegh, HL
- Date Issued
- 2008-12
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- Toll-like receptors (TLRs) activate the innate immune system in response to pathogens. Here we show that TLR9 proteolytic cleavage is a prerequisite for TLR9 signaling. Inhibition of lysosomal proteolysis rendered TLR9 inactive. The carboxy-terminal fragment of TLR9 thus generated included a portion of the TLR9 ectodomain, as well as the transmembrane and cytoplasmic domains. This cleavage fragment bound to the TLR9 ligand CpG DNA and, when expressed in Tlr9(-/-) dendritic cells, restored CpG DNA-induced cytokine production. Although cathepsin L generated the requisite TLR9 cleavage products in a cell-free in vitro system, several proteases influenced TLR9 cleavage in intact cells. Lysosomal proteolysis thus contributes to innate immunity by facilitating specific cleavage of TLR9.
- Keywords
- ANTIGEN PRESENTATION; PATTERN-RECOGNITION; CATHEPSIN-L; PATHWAY; TLR9; MICE; DNA; INDUCTION; COMPLEXES; MOLECULE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/26233
- DOI
- 10.1038/NI.1669PG 8
- ISSN
- 1529-2908
- Article Type
- Article
- Citation
- NATURE IMMUNOLOGY, vol. 9, no. 12, page. 1407 - 1414, 2008-12
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