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Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9.

Park, Boyoun and Brinkmann, Melanie M and Spooner, Eric and Lee, Clarissa C and 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
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 13:48
Last Modified: 14 Dec 2009 13:48
URI: https://oak.novartis.com/id/eprint/1361

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