BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells.

ABSTRACT: Toll-like receptors (TLR) are essential components of the innate immune system. Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1⁺ late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-κB activation and TNF production upon DNA detection. An inducible VAMP3^+/LAMP2^+/LAMP1^- endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and consequent downstream signalling events. Conversely, sustained BAD-LAMP expression in pDCs contributes to their lack of type

SUBMITTER: Combes A 

PROVIDER: S-EPMC5640662 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature