RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response.

Abstract

RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs human beta defensin 2 and LL-37 promote the toll-like receptor 9-mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. The stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase in the production of IP-10. Of note, the stimulation of keratinocytes with human beta defensin 2 and LL-37 in combination with DNA failed to induce the production of IP-10. The production of IP-10 was mediated by the induction of the type I interferon IFN-β and was significantly downregulated by blocking of the interferon-α/β receptor and inhibition of stimulator of IFN genes. In addition, the pretreatment of keratinocytes with RNase 7 and DNA significantly reduced the herpes simplex virus-1 infection of human keratinocytes. This study demonstrates that RNase 7 functions as an alarmin by converting self-DNA into a danger signal that directly activates an antiviral immune response in human keratinocytes without the involvement of plasmacytoid dendritic cells.

• Authors: Verena Kopfnagel, Sylvia Dreyer, Kathrin Baumert, Maximilian Stark, Jürgen Harder, Karsten Hofmann, Michael Kleine, Anna Buch, Beate Sodeik, Thomas Werfel
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 140 Issue 8 Pg. 1589-1598.e3 (08 2020) ISSN: 1523-1747 [Electronic] United States
• PMID: 31978413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Alarmins
• CXCL10 protein, human
• Chemokine CXCL10
• DNA
• Ribonucleases
• Ribonuclease 7

Topics

• Alarmins (metabolism)
• Cells, Cultured
• Chemokine CXCL10 (metabolism)
• DNA (metabolism)
• Herpes Simplex (immunology, virology)
• Herpesvirus 1, Human (immunology)
• Host Microbial Interactions (immunology)
• Humans
• Immunity, Innate
• Keratinocytes (immunology, metabolism)
• Primary Cell Culture
• Ribonucleases (metabolism)