TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.

Localization of Toll-like receptors (TLR) in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TL...

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Autores principales:	Karim J Brandt, Céline Fickentscher, Egbert K O Kruithof, Philippe de Moerloose
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/069241185f374cc58c2e12173649df8a
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spelling	oai:doaj.org-article:069241185f374cc58c2e12173649df8a2021-11-18T08:42:19ZTLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.1932-620310.1371/journal.pone.0080743https://doaj.org/article/069241185f374cc58c2e12173649df8a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349012/?tool=EBIhttps://doaj.org/toc/1932-6203Localization of Toll-like receptors (TLR) in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell line, despite the expression of TLR2 at the cell surface. Further analyses indicate that TLR2-induced NF-κB activation is controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14 serves as an important upstream regulator. These findings establish that internalization of cell-surface TLR2 into endosomal compartments is required for NF-κB activation. These observations further demonstrate the need of endocytosis in the activation and regulation of TLR2-dependent signaling pathways.Karim J BrandtCéline FickentscherEgbert K O KruithofPhilippe de MoerloosePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e80743 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karim J Brandt Céline Fickentscher Egbert K O Kruithof Philippe de Moerloose TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.
description	Localization of Toll-like receptors (TLR) in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell line, despite the expression of TLR2 at the cell surface. Further analyses indicate that TLR2-induced NF-κB activation is controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14 serves as an important upstream regulator. These findings establish that internalization of cell-surface TLR2 into endosomal compartments is required for NF-κB activation. These observations further demonstrate the need of endocytosis in the activation and regulation of TLR2-dependent signaling pathways.
format	article
author	Karim J Brandt Céline Fickentscher Egbert K O Kruithof Philippe de Moerloose
author_facet	Karim J Brandt Céline Fickentscher Egbert K O Kruithof Philippe de Moerloose
author_sort	Karim J Brandt
title	TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.
title_short	TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.
title_full	TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.
title_fullStr	TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.
title_full_unstemmed	TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.
title_sort	tlr2 ligands induce nf-κb activation from endosomal compartments of human monocytes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/069241185f374cc58c2e12173649df8a
work_keys_str_mv	AT karimjbrandt tlr2ligandsinducenfkbactivationfromendosomalcompartmentsofhumanmonocytes AT celinefickentscher tlr2ligandsinducenfkbactivationfromendosomalcompartmentsofhumanmonocytes AT egbertkokruithof tlr2ligandsinducenfkbactivationfromendosomalcompartmentsofhumanmonocytes AT philippedemoerloose tlr2ligandsinducenfkbactivationfromendosomalcompartmentsofhumanmonocytes
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TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.

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