Toll Like Receptor 7/8 (TLR7/8) Cascade

Stable Identifier
Homo sapiens
Related Species
Influenza A virus, Human immunodeficiency virus 1, Human SARS coronavirus
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

RNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1), for example, stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokine (Heil F et al. 2004). This has been found to be mediated by TLR7, as well as TLR8. Similarly, severe acute respiratory syndrome-associated coronavirus (SARS-CoV) ssRNAs had powerful immunostimulatory activities in mononuclear phagocytes to induce considerable level of pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8 (Li Y et al. 2013). Moreover, SARS-CoV ssRNA was able to cause acute lung injury in mice with a high mortality rate in vivo experiment. It suggests that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine storm associated with a dysregulation of the innate immunity (Li Y et al. 2013). Separate studies showed that imidazoquinoline compounds (e.g. imiquimod and R-848, low-molecular-weight immune response modifiers that can induce the synthesis of interferon-alpha) also exert their effects in a MyD88-dependent fashion independently through TLR7 and 8 (Hemmi H et al. 2002; Jurk M et al. 2002; Diebold SS et al. 2004). TLR7 and TLR8 are endosomal receptors that sense viral ssRNA in the phagocytic lumen. Their activation leads to NF-κB-, AP1- and IFN regulatory factor (IRF)-mediated production of type I IFNs (IFN-α/β) and pro-inflammatory cytokines.

Literature References
PubMed ID Title Journal Year
14976262 Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8

Heil, F, Hemmi, H, Hochrein, H, Ampenberger, F, Kirschning, C, Akira, S, Lipford, G, Wagner, H, Bauer, S

Science 2004
Participant Of
Event Information
Orthologous Events
Cite Us!