Toll-Like Receptor (TLR) & Innate Sensing
Toll-like receptors are the innate immune system's pattern-recognition front line. Surface receptors read bacterial products — TLR4 with CD14 and MD-2 senses LPS, TLR2 heterodimerises with TLR1 or TLR6 for lipopeptides, TLR5 binds flagellin — while endosomal TLR3, TLR7 and TLR9 sample nucleic acids. Every receptor except TLR3 signals through MyD88 (with TIRAP bridging TLR4 and TLR2), driving IRAK4, IRAK1, TRAF6 and TAK1 into the IKKβ/NEMO complex, which frees NF-κB from its IκBα brake, and into p38/JNK to activate AP-1. TLR3 and TLR4 additionally recruit TRIF, which with TRAF3 activates TBK1 and IRF3; in plasmacytoid dendritic cells TLR7 and TLR9 route through MyD88 to IRF7. The two arms split the output: NF-κB and AP-1 drive TNF-α, IL-6 and IL-1β, while IRF3 and IRF7 drive IFN-β. A20 restrains TRAF6 to stop the response running away. Click any protein for the matching Assay Genie In Vivo antibody or ELISA kit.
Sensing: surface versus endosome. The TLR family splits by compartment and by ligand chemistry. At the plasma membrane, TLR4 needs two accessory proteins to read lipopolysaccharide — CD14 concentrates LPS and hands it to the TLR4–MD-2 complex, which is the actual LPS-binding unit. TLR2 is a promiscuous sensor that must heterodimerise, pairing with TLR1 for triacylated lipopeptides and TLR6 for diacylated ones, and TLR5 reads bacterial flagellin. Inside endosomes, TLR3 binds double-stranded RNA, TLR7 single-stranded RNA and TLR9 unmethylated CpG DNA — a compartment restriction that keeps nucleic-acid sensing away from the cell's own genome.
Two adaptors, two outputs. Every TLR except TLR3 signals through MyD88, with TIRAP (Mal) acting as the bridging adaptor for TLR4 and TLR2. MyD88 nucleates the Myddosome, activating IRAK4 then IRAK1, which ubiquitinates TRAF6 and activates TAK1. TAK1 then splits the signal: into the IKKβ/NEMO complex, which phosphorylates IκBα for degradation and so releases NF-κB, and into p38 and JNK, which activate AP-1. TLR3 and TLR4 instead recruit TRIF, which with TRAF3 activates TBK1 to phosphorylate IRF3; in plasmacytoid dendritic cells, TLR7 and TLR9 run a MyD88-dependent route to IRF7. TRIF also feeds TRAF6, so the interferon arm contributes to NF-κB as well.
Brakes and the In Vivo tie-in. The response is self-limiting: A20 (TNFAIP3) is itself an NF-κB target that deubiquitinates TRAF6, and resynthesised IκBα recaptures NF-κB — both measurable by ELISA and both worth quantifying when a TLR agonist response looks unexpectedly brief. The pathway's output is where the In Vivo functional-grade range acts: In Vivo anti-TNF-α and anti-IL-1β neutralise the two cytokines that drive most of the pathology in LPS and TLR-agonist models, letting you separate a cytokine's contribution from the sensing event upstream, while IL-6 and IFN-β ELISA kits read the NF-κB and IRF arms independently of one another. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — In Vivo antibody, ELISA kit or research antibody.