Neutrophils express distinct RNA receptors in a non-canonical way

Michael Berger, Chin Yuan Hsieh, Martina Bakele, Veronica Marcos, Nikolaus Rieber, Michael Kormann, Lauren Mays, Laura Hofer, Olaf Neth, Ljubomir Vitkov, Wolf Dietrich Krautgartner, Dietrich Von Schweinitz, Roland Kappler, Andreas Hector, Alexander Weber, Dominik Hartl

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

RNAs are capable of modulating immune responses by binding to specific receptors. Neutrophils represent the major fraction of circulating immune cells, but receptors and mechanisms by which neutrophils sense RNA are poorly defined. Here, we analyzed the mRNA and protein expression patterns and the subcellular localization of the RNA receptors RIG-I, MDA-5, TLR3, TLR7, and TLR8 in primary neutrophils and immortalized neutrophil-like differentiated HL-60 cells. Our results demonstrate that both neutrophils and differentiated HL-60 cells express RIG-I, MDA-5, and TLR8 at themRNAand protein levels, whereas TLR3 and TLR7 are not expressed at the protein level. Subcellular fractionation, flow cytometry, confocal laser scanning microscopy, and immuno-transmission electron microscopy provided evidence that, besides the cytoplasm, RIG-I and MDA-5 are stored in secretory vesicles of neutrophils and showed that RIG-I and its ligand, 3p-RNA, co-localize at the cell surface without triggering neutrophil activation. In summary, this study demonstrates that neutrophils express a distinct pattern of RNA recognition receptors in a non-canonical way, which could have essential implications for future RNAbased therapeutics.

Original languageEnglish
Pages (from-to)19409-19417
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number23
DOIs
StatePublished - 1 Jun 2012
Externally publishedYes

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