AI Article Synopsis
- The study investigates how single-stranded oligonucleotides (ssON) inhibit the endocytic pathways necessary for Toll-like receptor (TLR) signaling, which is crucial for immune response against pathogens.
- ssON interference is RNA or DNA dependent, relies on the specific length of the oligonucleotide, and affects the signaling of TLR3, TLR4, and TLR7.
- Injecting ssON in primates reduces inflammatory responses triggered by double-stranded RNA, highlighting their role in regulating immune reactions and preventing excessive inflammation.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203749 | PMC |
| http://dx.doi.org/10.1038/s41598-018-33960-4 | DOI Listing |
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