BioLegend Innate Signaling
Innate Immune Signaling: Pattern Recognition Receptors
Infection or tissue injury causes innate immune cells such as Dendritic cells, Macrophages, and Neutrophils, to recognize pathogen-associated molecular patterns (PAMPs) or host derived damage-associated molcular patterns (DAMPs) via pattern recognition receptors (PRRs) on the cell surface and in the cytoplasm. The major PRRs on cells include Toll-Like receptors (TLRs), NOD-like receptors (NLRs), and retinoic acid-inducible gene 1 (RIG-I) like receptors (RLRs). BioLegend offers variety of reagents to study these pathways for innate immune cell signaling.

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Toll-Like Receptor Signaling
TLRs are the best studied family of PRRs, which recognize PAMPs of diverse pathogens including bacteria (Gram-positive and Gram-negative), DNA and RNA viruses, parasites, protozoa, and fungi. TLRs are broadly subdivided based on their location at the cell surface (these are activated by lipid and protein ligands) and endosomal compartments (these are activated by non-self nucleic acids).

TLRs typically dimerize upon ligand binding and their cytoplasmic domain called Toll/IL-1 (TIR, due to similarities to the IL-1 receptor) then serves as a docking site for TIR containing adaptor proteins. Out of several intracellular TIR containing proteins such as TRIF, TIRAP and TRAM, MyD88 acts a central player in innate immune signaling by being the canonical adaptor for inflammatory signaling pathways downstream of TLRs (except TLR3, which signals via TRIF), as well as IL-1 receptor families. MyD88 binds directly to the majority of TLR TIRs but in some cases the binding occurs in combination with adaptor TIRAP. MyD88 then recruits IRAK1 and IRAK4, which are later dissociated after being phosphorylated. The MyD88–IRAK complex also interacts with ubiquitin ligase TRAF6 to make polyubiquitin chains that activate the IKK complex for NF-κB and MAPK dependent gene transcription and production of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and IL-12, and TNF-α. In addition, via the activation of interferon regulatory factor (IRF), MyD88 can also stimulate type 1 IFN genes leading to the production of antiviral interferons such as IFN-α , IFN-β, and IFN-λ

To view a step-by-step guide of the TLR signaling pathways, start the presentation below. (Best viewed in full screen mode. Use the [ ] icon at the bottom right.)

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Click the image below for an overview of the TLR signaling pathways.

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