Toll-like receptors (TLR), Nucleotide-binding oligomerization domain-like receptors (NLR), and Stimulator of interferon genes (STING) (TLR/NLR/STING)

The Toll-like receptors (TLRs), Nucleotide-binding oligomerization domain-like receptors (NLRs), and Stimulator of interferon genes (STING) represent the primary axes of innate immune pattern recognition. TLRs are membrane-bound receptors that identify extracellular and endosomal threats, such as bacterial lipids and viral RNAs (Kawai & Akira, Nat Immunol 2010; Medzhitov, Nat Rev Immunol 2001). NLRs function as intracellular sensors, with several members forming inflammasomes that process interleukin-1 family cytokines in response to cellular stress or infection (Schroder & Tschopp, Cell 2010). STING acts as a central adaptor in the cGAS-STING pathway, detecting cytosolic DNA to induce a robust type I interferon response (Ishikawa & Barber, Nature 2008). From a therapeutic perspective, these pathways are being aggressively targeted to modulate the immune microenvironment. Agonists for TLRs and STING are currently in clinical development to convert "cold" tumors into immunologically "hot" ones, thereby improving the efficacy of checkpoint inhibitors (Barber, Nat Rev Immunol 2015). Conversely, inhibitors of NLRs (specifically NLRP3) and STING are being explored to mitigate hyper-inflammation in conditions like gout and various autoimmune disorders (Motta et al., FEBS J 2015).

Other names

Pattern recognition receptorsPRRsInnate immune sensorscGAS-STING pathway componentsInflammasome components

Agonism of these pathways is utilized to enhance anti-tumor immunity and vaccine responses, while antagonism is employed to suppress pathological inflammation in autoimmune and autoinflammatory disorders.