Toll-like Receptors (TLRs) Overview

Study Notes

TLRs are a family of transmembrane proteins that are involved in the innate immune response. They are highly conserved across species and recognize pathogen-associated molecular patterns (PAMPs) on pathogens.
TLRs are found on the cell surface and in endosomes.
TLRs recognize PAMPs through leucine-rich repeats (LRRs) in their extracellular domain.
TLRs signal through the Toll/IL-1R (TIR) domain in their intracellular domain.
TLRs are important for the recognition of pathogens and the activation of the innate immune response.
TLRs signal through two main pathways: MyD88-dependent and MyD88-independent.
TLR1, TLR2, TLR4 and TLR6 recognize lipids and lipoproteins from bacteria.
TLR3, TLR7, TLR8, and TLR9 recognize nucleic acids from viruses and bacteria.
TLR4 recognizes lipopolysaccharide (LPS) from Gram-negative bacteria through MD2 and CD14.
TLR5 recognizes bacterial flagellin.
TLR10 binds dsRNA in vitro at endosomal pH.
TLR signaling leads to inflammatory cytokine production.

NLRs are intracellular proteins that recognize PAMPs and DAMPs in the cytoplasm.
NLRs contain a leucine-rich repeat (LRR) domain, a nucleotide-binding oligomerization domain (NOD), and N-terminal effector domains.
NLRs signal through the NOD domain.
NLRs often form oligomers when activated.
NLRs activate NF-κB and MAPK pathways.
NLRP3 forms the inflammasome.
NLRP3 activates caspase-1 and initiates pyroptosis.
NLRP3 is involved in the recognition of a variety of pathogens and danger signals
NOD1 and NOD2 recognize bacterial peptidoglycans.
NOD1 and NOD2 are located in the cytoplasm, but can be recruited to the plasma membrane and endosomal membrane.
Palmitoylation of NOD1/2 is important for their recruitment to the membrane.

RLRs are cytoplasmic receptors that recognize viral RNA.
RLRs contain a caspase recruitment domain (CARD), a DExD/H-box helicase domain, and a C-terminal regulatory domain.
RLRs signal through the CARD domain.
RIG-I recognizes short, 5'-triphosphate dsRNA.
MDA5 recognizes long dsRNA.
LGP2 is an adapter protein that interacts with RIG-I and MDA5.
LGP2 can enhance MDA5-mediated signaling.
RLR signaling activates NF-κB and IRF3, leading to the production of type I interferons.

CLRs are cell surface receptors that recognize carbohydrates on pathogens. These receptors are involved in the recognition of pathogens and the activation of the innate immune response.
CLRs have carbohydrate recognition domains (CRDs) that bind to carbohydrates.
CLRs can be transmembrane or secretory receptors.
CLRs are involved in antigen presentation, the activation of innate immune cells, and the induction of inflammation.
CLRs can be divided into type I and type II based on their topological structure.