Park, Boyoun, Brinkmann, Melanie M, Spooner, Eric, Lee, Clarissa C, Kim, You-Me and Ploegh, Hidde L (2008) Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9. Nature Immunology, 9 (12). pp. 1407-1414. ISSN 1529-2916

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... http://www.pubmedcentral.nih.gov/article...
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... http://www.pubmedcentral.nih.gov/article...
Date Deposited:	14 Dec 2009 13:48
Last Modified:	14 Dec 2009 13:48
URI:	https://oak.novartis.com/id/eprint/1361