Release of the Pre-Assembled naRNA-LL37 Composite DAMP Re-Defines Neutrophil Extracellular Traps (NETs) as Intentional DAMP Webs

Bork, Francesca; Greve, Carsten  Leo; Youn, Christine; Chen, Sirui; Wang, Yu; Nasri, Masoud; Focken, Jule; Scheurer, Jasmin; Engels, Pujan; Dubbelaar, Marissa L.; Hipp, Katharina; Schittek, Birgit; Bugl, Stefanie; Löffler, Markus; Skokowa, Julia; Archer, Nick; Weber, Alexander N.R.

doi:10.2139/ssrn.4244243

Cited by 1 publication

(3 citation statements)

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“…Psoriasis is an inflammatory skin disease with strong polymorphonuclear neutrophil infiltration. Sensing NET-associated RNAs by TLR8 in humans and Tlr13 in mice contributes to skin inflammation and progression of psoriasis 38,39 . IFN-Is play an important role in the pathogenesis of systemic sclerosis, a multisystem life-threatening inflammatory and fibrotic disorder 102–104 .…”

Section: Tlr8 and Diseasesmentioning

confidence: 99%

“…Thus, mTlr8 does not have the ability to recognize hTLR8 ssRNA and chemical ligands. Unlike TLR7, which senses guanosine (G)-rich ssRNAs and G-modified derivatives, 33 the natural ligands of TLR8 are uridine (U)-rich ssRNAs from microbial pathogens, 12,31,33–37 and self-derived RNA such as neutrophil extracellular trap (NET)–associated RNA 38,39 . Similar to mTlr13, hTLR8 is also capable of detecting fragments derived from bacterial 23S ribosomal RNA and self-mitochondrial RNA sequence–derived oligoribonucleotides (ORNs).…”

Section: Ligands Recognized By Tlr8mentioning

confidence: 99%

“…Those chaperone molecules are normally short cationic molecules, such as LL37 and high mobility group box protein 1 (HMGB1), which bind NAs via charge:charge interactions 72–77 . Neutrophil extracellular trap–associated RNA in complex with LL37 amplifies TLR8 responses in PBMCs 38,39 . Chaperone molecules are involved in and amplify eTLR responses in inflammatory diseases 62,78–80 .…”

Section: Tlr8 Signaling Crosstalk With Other Moleculesmentioning

confidence: 99%

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A Biological Perspective of TLR8 Signaling in Host Defense and Inflammation

Bian

Dong

Wu³

et al. 2023

Infect Microb Dis

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Toll-like receptors (TLRs) play important roles in immune responses against pathogens and tumors. Recently, TLR8 has gained attention because of its association with multiple inflammatory diseases, infections and antitumor responses. TLR8 senses the degradation products of single-stranded RNA from microbes and self-released RNA to induce type I interferons, inflammatory gene expression and nucleotide-binding and oligomerization domain-, leucine-rich repeat-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. So far, the understanding of TLR8 function in vivo is still limited, partially because of lacking a reliable rodent animal model. Murine Tlr8 cannot sense the ligands of human TLR8. In mammals, TLR8 distinguishes live bacteria from dead bacteria to regulate the magnitude of immune responses. Recently, TLR8 has been reported to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA to induce inflammatory responses, suggesting that TLR8 participates in coronavirus disease 2019 . In this review, we discuss the mechanism of ligand recognition by TLR8, TLR8-mediated signaling pathways and signaling crosstalk between TLR8 and other molecules, and untangle the contribution of TLR8 to inflammatory diseases, infectious diseases, antitumor immunity and vaccination.

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Section: Tlr8 and Diseasesmentioning

confidence: 99%