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- W4206145022 abstract "Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids. PMID: 18820679 Funding information This work was supported by: NIAID NIH HHS, United States Grant ID: R01 AI072429 NIAID NIH HHS, United States Grant ID: R01 AI072429-01A2 NIAID NIH HHS, United States Grant ID: AI072429 NCI NIH HHS, United States Grant ID: CA009179 NCI NIH HHS, United States Grant ID: T32 CA009179 NHLBI NIH HHS, United States Grant ID: HL67204 NHLBI NIH HHS, United States Grant ID: R37 HL067204 More Less keyboard_arrow_down" @default.
- W4206145022 created "2022-01-25" @default.
- W4206145022 creator A5063233755 @default.
- W4206145022 date "2008-12-02" @default.
- W4206145022 modified "2023-09-27" @default.
- W4206145022 title "Faculty Opinions recommendation of The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor." @default.
- W4206145022 doi "https://doi.org/10.3410/f.1127786.589924" @default.
- W4206145022 hasPublicationYear "2008" @default.
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