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Article Dans Une Revue Nature Communications Année : 2017

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

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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 I interferon production after exposure to a TGF-β-positive microenvironment or isolation from human breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly, by promoting TLR9 sorting to late endosome compartments at steady state and in response to immunomodulatory cues.
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hal-03545468 , version 1 (27-01-2022)

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Alexis Combes, Voahirana Camosseto, Prudence N’guessan, Rafael J Argüello, Julie Mussard, et al.. BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells. Nature Communications, 2017, 8 (1), pp.913. ⟨10.1038/s41467-017-00695-1⟩. ⟨hal-03545468⟩
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