Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis

Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocy...
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Autor*in:	Peter Järver [verfasserIn] Aleksandra Dondalska [verfasserIn] Candice Poux [verfasserIn] AnnSofi Sandberg [verfasserIn] Joseph Bergenstråhle [verfasserIn] Annette E. Sköld [verfasserIn] Nathalie Dereuddre-Bosquet [verfasserIn] Fréderic Martinon [verfasserIn] Sandra Pålsson [verfasserIn] Eman Zaghloul [verfasserIn] David Brodin [verfasserIn] Birgitta Sander [verfasserIn] Kim A. Lennox [verfasserIn] Mark A. Behlke [verfasserIn] Samir EL-Andaloussi [verfasserIn] Janne Lehtiö [verfasserIn] Joakim Lundeberg [verfasserIn] Roger LeGrand [verfasserIn] Anna-Lena Spetz [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 8(2018), 1, Seite 17
Übergeordnetes Werk:	volume:8 ; year:2018 ; number:1 ; pages:17

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-018-33960-4

Katalog-ID:	DOAJ008661448

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allfields	10.1038/s41598-018-33960-4 doi (DE-627)DOAJ008661448 (DE-599)DOAJ8ee60f6cd9e941b7b20a1654b77636dc DE-627 ger DE-627 rakwb eng Peter Järver verfasserin aut Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses. Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation Medicine R Science Q Aleksandra Dondalska verfasserin aut Candice Poux verfasserin aut AnnSofi Sandberg verfasserin aut Joseph Bergenstråhle verfasserin aut Annette E. Sköld verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Fréderic Martinon verfasserin aut Sandra Pålsson verfasserin aut Eman Zaghloul verfasserin aut David Brodin verfasserin aut Birgitta Sander verfasserin aut Kim A. Lennox verfasserin aut Mark A. Behlke verfasserin aut Samir EL-Andaloussi verfasserin aut Janne Lehtiö verfasserin aut Joakim Lundeberg verfasserin aut Roger LeGrand verfasserin aut Anna-Lena Spetz verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 17 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:17 https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/article/8ee60f6cd9e941b7b20a1654b77636dc kostenfrei https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 17
spelling	10.1038/s41598-018-33960-4 doi (DE-627)DOAJ008661448 (DE-599)DOAJ8ee60f6cd9e941b7b20a1654b77636dc DE-627 ger DE-627 rakwb eng Peter Järver verfasserin aut Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses. Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation Medicine R Science Q Aleksandra Dondalska verfasserin aut Candice Poux verfasserin aut AnnSofi Sandberg verfasserin aut Joseph Bergenstråhle verfasserin aut Annette E. Sköld verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Fréderic Martinon verfasserin aut Sandra Pålsson verfasserin aut Eman Zaghloul verfasserin aut David Brodin verfasserin aut Birgitta Sander verfasserin aut Kim A. Lennox verfasserin aut Mark A. Behlke verfasserin aut Samir EL-Andaloussi verfasserin aut Janne Lehtiö verfasserin aut Joakim Lundeberg verfasserin aut Roger LeGrand verfasserin aut Anna-Lena Spetz verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 17 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:17 https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/article/8ee60f6cd9e941b7b20a1654b77636dc kostenfrei https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 17
allfields_unstemmed	10.1038/s41598-018-33960-4 doi (DE-627)DOAJ008661448 (DE-599)DOAJ8ee60f6cd9e941b7b20a1654b77636dc DE-627 ger DE-627 rakwb eng Peter Järver verfasserin aut Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses. Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation Medicine R Science Q Aleksandra Dondalska verfasserin aut Candice Poux verfasserin aut AnnSofi Sandberg verfasserin aut Joseph Bergenstråhle verfasserin aut Annette E. Sköld verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Fréderic Martinon verfasserin aut Sandra Pålsson verfasserin aut Eman Zaghloul verfasserin aut David Brodin verfasserin aut Birgitta Sander verfasserin aut Kim A. Lennox verfasserin aut Mark A. Behlke verfasserin aut Samir EL-Andaloussi verfasserin aut Janne Lehtiö verfasserin aut Joakim Lundeberg verfasserin aut Roger LeGrand verfasserin aut Anna-Lena Spetz verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 17 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:17 https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/article/8ee60f6cd9e941b7b20a1654b77636dc kostenfrei https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 17
allfieldsGer	10.1038/s41598-018-33960-4 doi (DE-627)DOAJ008661448 (DE-599)DOAJ8ee60f6cd9e941b7b20a1654b77636dc DE-627 ger DE-627 rakwb eng Peter Järver verfasserin aut Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses. Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation Medicine R Science Q Aleksandra Dondalska verfasserin aut Candice Poux verfasserin aut AnnSofi Sandberg verfasserin aut Joseph Bergenstråhle verfasserin aut Annette E. Sköld verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Fréderic Martinon verfasserin aut Sandra Pålsson verfasserin aut Eman Zaghloul verfasserin aut David Brodin verfasserin aut Birgitta Sander verfasserin aut Kim A. Lennox verfasserin aut Mark A. Behlke verfasserin aut Samir EL-Andaloussi verfasserin aut Janne Lehtiö verfasserin aut Joakim Lundeberg verfasserin aut Roger LeGrand verfasserin aut Anna-Lena Spetz verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 17 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:17 https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/article/8ee60f6cd9e941b7b20a1654b77636dc kostenfrei https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 17
allfieldsSound	10.1038/s41598-018-33960-4 doi (DE-627)DOAJ008661448 (DE-599)DOAJ8ee60f6cd9e941b7b20a1654b77636dc DE-627 ger DE-627 rakwb eng Peter Järver verfasserin aut Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses. Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation Medicine R Science Q Aleksandra Dondalska verfasserin aut Candice Poux verfasserin aut AnnSofi Sandberg verfasserin aut Joseph Bergenstråhle verfasserin aut Annette E. Sköld verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Fréderic Martinon verfasserin aut Sandra Pålsson verfasserin aut Eman Zaghloul verfasserin aut David Brodin verfasserin aut Birgitta Sander verfasserin aut Kim A. Lennox verfasserin aut Mark A. Behlke verfasserin aut Samir EL-Andaloussi verfasserin aut Janne Lehtiö verfasserin aut Joakim Lundeberg verfasserin aut Roger LeGrand verfasserin aut Anna-Lena Spetz verfasserin aut In Scientific Reports Nature Portfolio, 2011 8(2018), 1, Seite 17 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:8 year:2018 number:1 pages:17 https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/article/8ee60f6cd9e941b7b20a1654b77636dc kostenfrei https://doi.org/10.1038/s41598-018-33960-4 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2018 1 17
language	English
source	In Scientific Reports 8(2018), 1, Seite 17 volume:8 year:2018 number:1 pages:17
sourceStr	In Scientific Reports 8(2018), 1, Seite 17 volume:8 year:2018 number:1 pages:17
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation Medicine R Science Q
isfreeaccess_bool	true
container_title	Scientific Reports
authorswithroles_txt_mv	Peter Järver @@aut@@ Aleksandra Dondalska @@aut@@ Candice Poux @@aut@@ AnnSofi Sandberg @@aut@@ Joseph Bergenstråhle @@aut@@ Annette E. Sköld @@aut@@ Nathalie Dereuddre-Bosquet @@aut@@ Fréderic Martinon @@aut@@ Sandra Pålsson @@aut@@ Eman Zaghloul @@aut@@ David Brodin @@aut@@ Birgitta Sander @@aut@@ Kim A. Lennox @@aut@@ Mark A. Behlke @@aut@@ Samir EL-Andaloussi @@aut@@ Janne Lehtiö @@aut@@ Joakim Lundeberg @@aut@@ Roger LeGrand @@aut@@ Anna-Lena Spetz @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	663366712
id	DOAJ008661448
language_de	englisch
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author	Peter Järver
spellingShingle	Peter Järver misc Clathrin-mediated Endocytosis (CME) misc Endosomal TLR misc Endocytic Uptake misc Signaling Endosomes misc Inhibiting TLR4 Activation misc Medicine misc R misc Science misc Q Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
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topic_title	Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis Clathrin-mediated Endocytosis (CME) Endosomal TLR Endocytic Uptake Signaling Endosomes Inhibiting TLR4 Activation
topic	misc Clathrin-mediated Endocytosis (CME) misc Endosomal TLR misc Endocytic Uptake misc Signaling Endosomes misc Inhibiting TLR4 Activation misc Medicine misc R misc Science misc Q
topic_unstemmed	misc Clathrin-mediated Endocytosis (CME) misc Endosomal TLR misc Endocytic Uptake misc Signaling Endosomes misc Inhibiting TLR4 Activation misc Medicine misc R misc Science misc Q
topic_browse	misc Clathrin-mediated Endocytosis (CME) misc Endosomal TLR misc Endocytic Uptake misc Signaling Endosomes misc Inhibiting TLR4 Activation misc Medicine misc R misc Science misc Q
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title	Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
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title_full	Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
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author_browse	Peter Järver Aleksandra Dondalska Candice Poux AnnSofi Sandberg Joseph Bergenstråhle Annette E. Sköld Nathalie Dereuddre-Bosquet Fréderic Martinon Sandra Pålsson Eman Zaghloul David Brodin Birgitta Sander Kim A. Lennox Mark A. Behlke Samir EL-Andaloussi Janne Lehtiö Joakim Lundeberg Roger LeGrand Anna-Lena Spetz
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title_sort	single-stranded nucleic acids regulate tlr3/4/7 activation through interference with clathrin-mediated endocytosis
title_auth	Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
abstract	Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
abstractGer	Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
abstract_unstemmed	Abstract Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
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title_short	Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
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Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis

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