Abstract
Toll‐like receptor 7 (TLR7) is an innate immune sensor for single‐strand RNA (ssRNA). Recent structural analysis revealed that TLR7 has an additional binding site for nucleosides such as guanosine, and is activated when both guanosine and ssRNA bind. The nucleoside binding site also accommodates imidazoquinoline derivatives such as R848, which activate TLR7 in the absence of ssRNA. Here, we report that deoxyguanosine (dG) triggered cytokine production in murine bone marrow derived macrophages and plasmacytoid dendritic cells, as well as in human peripheral blood mononuclear cells, including type I interferons and pro‐inflammatory factors such as TNF and IL‐6. This signalling activity of dG was dependent on TLR7 and its adaptor MyD88 and did not require amplification via the type I interferon receptor. dG‐triggered cytokine production required endosomal maturation but did not depend on the concurrent provision of RNA. We conclude that dG induces an inflammatory response through TLR7 and propose that dG is an RNA‐independent TLR7 agonist.
Highlights
PRRs are germline encoded proteins that recognise PAMPs and/or danger-associated molecular patterns
Toll-like receptor 7 (TLR7) was first reported to be activated by imidazoquinoline compounds and guanosine analogues [3,4,5,6], it is best known as a sensor of single strand RNAs of viral or self-origin and recognises uridine ribonucleotides in single-strand RNA (ssRNA) [7,8,9]
Variability between donors may be related to the frequency of TLR7-expressing cells such as plasmacytoid dendritic cells · purine nucleoside phosphorylase (PNP) (pDC), which is known to vary between individuals [14]
Summary
Toll-like receptor 7 (TLR7) is an innate immune sensor for single-strand RNA (ssRNA). Recent structural analysis revealed that TLR7 has an additional binding site for nucleosides such as guanosine, and is activated when both guanosine and ssRNA bind. We report that deoxyguanosine (dG) triggered cytokine production in murine bone marrow derived macrophages and plasmacytoid dendritic cells, as well as in human peripheral blood mononuclear cells, including type I interferons and pro-inflammatory factors such as TNF and IL-6. This signalling activity of dG was dependent on TLR7 and its adaptor MyD88 and did not require amplification via the type I interferon receptor. Additional supporting information may be found online in the Supporting Information section at the end of the article
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