Ostendorf, Thomas, Zillinger, Thomas ORCID: 0000-0002-0866-4835, Andryka, Katarzyna, Schlee-Guimaraes, Thais Marina, Schmitz, Saskia, Marx, Samira, Bayrak, Kubra, Linke, Rebecca, Salgert, Sarah, Wegner, Julia, Grasser, Tatjana, Bauersachs, Sonja, Soltesz, Leon, Huebner, Marc P., Nastaly, Maximilian, Coch, Christoph, Kettwig, Matthias, Roehl, Ingo, Henneke, Marco, Hoerauf, Achim, Barchet, Winfried ORCID: 0000-0002-6745-6606, Gaertner, Jutta, Schlee, Martin, Hartmann, Gunther and Bartok, Eva ORCID: 0000-0003-0556-1950 (2020). Immune Sensing of Synthetic, Bacterial, and Protozoan RNA by Toll-like Receptor 8 Requires Coordinated Processing by RNase T2 and RNase 2. Immunity, 52 (4). S. 591 - 612. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Human toll-like receptor 8 (TLR8) activation induces a potent T helper-1 (Th1) cell response critical for defense against intracellular pathogens, including protozoa. The receptor harbors two distinct binding sites, uridine and di- and/or trinucleotides, but the RNases upstream of TLR8 remain poorly characterized. We identified two endolysosomal endoribonucleases, RNase T2 and RNase 2, that act synergistically to release uridine from oligoribonucleotides. RNase T2 cleaves preferentially before, and RNase 2 after, uridines. Live bacteria, P. falciparum-infected red blood cells, purified pathogen RNA, and synthetic oligoribonucleotides all required RNase 2 and T2 processing to activate TLR8. Uridine supplementation restored RNA recognition in RNASE2(-/-) or RNASET2(-/-) but not RNASE2(-/-) RNASET2(-/-) cells. Primary immune cells from RNase T2-hypomorphic patients lacked a response to bacterial RNA but responded robustly to small-molecule TLR8 ligands. Our data identify an essential function of RNase T2 and RNase 2 upstream of TLR8 and provide insight into TLR8 activation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ostendorf, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zillinger, ThomasUNSPECIFIEDorcid.org/0000-0002-0866-4835UNSPECIFIED
Andryka, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlee-Guimaraes, Thais MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitz, SaskiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marx, SamiraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bayrak, KubraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linke, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salgert, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wegner, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grasser, TatjanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauersachs, SonjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soltesz, LeonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebner, Marc P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nastaly, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coch, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kettwig, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roehl, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henneke, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoerauf, AchimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barchet, WinfriedUNSPECIFIEDorcid.org/0000-0002-6745-6606UNSPECIFIED
Gaertner, JuttaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlee, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, GuntherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartok, EvaUNSPECIFIEDorcid.org/0000-0003-0556-1950UNSPECIFIED
URN: urn:nbn:de:hbz:38-337172
DOI: 10.1016/j.immuni.2020.03.009
Journal or Publication Title: Immunity
Volume: 52
Number: 4
Page Range: S. 591 - 612
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CYSTIC LEUKOENCEPHALOPATHY; STRANDED-RNA; TLR8; RECOGNITION; RIBONUCLEASES; FAMILY; EVOLUTION; MONOCYTES; ALPHA; CELLSMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33717

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