toll-like receptor 7 signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by a ligand binding to the endolysosomal toll-like receptor 7. [GOC:add, PMID:16551253, PMID:17328678]

Toll-like receptor 7 (TLR7) is a pattern recognition receptor (PRR) expressed primarily in endosomes of immune cells, including plasmacytoid dendritic cells (pDCs) and B cells. TLR7 plays a crucial role in the innate immune response by recognizing single-stranded RNA (ssRNA) molecules from viruses and other pathogens.

Upon encountering viral ssRNA, TLR7 undergoes a series of conformational changes, leading to its dimerization and activation. This activation triggers the recruitment of adaptor proteins, particularly MyD88, to the TLR7 complex. MyD88 serves as a signaling hub, initiating a cascade of downstream signaling events.

The MyD88-dependent pathway involves the activation of interleukin-1 receptor-associated kinase 4 (IRAK4), which phosphorylates IRAK1. This phosphorylation event leads to the formation of a complex containing IRAK1, IRAK2, and TRAF6, ultimately activating the transforming growth factor-β-activated kinase 1 (TAK1).

TAK1 activation leads to the phosphorylation and activation of two key transcription factors: nuclear factor-κB (NF-κB) and interferon regulatory factor 7 (IRF7). NF-κB translocates to the nucleus and induces the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-12 (IL-12). These cytokines contribute to the development of inflammation and the recruitment of immune cells.

IRF7, also activated by TAK1, translocates to the nucleus and promotes the transcription of type I interferons (IFNs), including IFN-α and IFN-β. These IFNs possess antiviral properties, inhibiting viral replication and enhancing the immune response.

Overall, the TLR7 signaling pathway is a critical component of innate immunity, recognizing viral ssRNA and triggering the production of pro-inflammatory cytokines and type I IFNs. These molecules activate downstream signaling pathways, leading to the elimination of viral pathogens and the establishment of antiviral immunity.'
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Proteins (2)

Compounds (12)