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| Item Type: | Article |
|---|---|
| Title: | Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia |
| Creators Name: | Wallach, T. and Raden, M. and Hinkelmann, L. and Brehm, M. and Rabsch, D. and Weidling, H. and Krüger, C. and Kettenmann, H. and Backofen, R. and Lehnardt, S. |
| Abstract: | INTRODUCTION: The pandemic coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is marked by thromboembolic events and an inflammatory response throughout the body, including the brain. METHODS: Employing the machine learning approach BrainDead we systematically screened for SARS-CoV-2 genome-derived single-stranded (ss) RNA fragments with high potential to activate the viral RNA-sensing innate immune receptors Toll-like receptor (TLR)7 and/or TLR8. Analyzing HEK TLR7/8 reporter cells we tested such RNA fragments with respect to their potential to induce activation of human TLR7 and TLR8 and to activate human macrophages, as well as iPSC-derived human microglia, the resident immune cells in the brain. RESULTS: We experimentally validated several sequence-specific RNA fragment candidates out of the SARS-CoV-2 RNA fragments predicted in silico as activators of human TLR7 and TLR8. Moreover, these SARS-CoV-2 ssRNAs induced cytokine release from human macrophages and iPSC-derived human microglia in a sequence- and species-specific fashion. DISCUSSION: Our findings determine TLR7 and TLR8 as key sensors of SARS-CoV-2-derived ssRNAs and may deepen our understanding of the mechanisms how this virus triggers, but also modulates an inflammatory response through innate immune signaling. |
| Keywords: | SARS-CoV-2, RNA, Toll-Like Receptors, iPSC-Derived Human Microglia, Macrophages, Inflammatory Response, Animals, Mice |
| Source: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media SA |
| Volume: | 13 |
| Page Range: | 1066456 |
| Date: | 13 January 2023 |
| Official Publication: | https://doi.org/10.3389/fimmu.2022.1066456 |
| PubMed: | View item in PubMed |
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