Pattern recognition receptors

Pattern Recognition Receptors (PRRs)

Innate immune receptors that recognize conserved Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs), triggering inflammatory responses via transcription factors NF-κB and IRFs.

• Toll-Like Receptors (TLRs)

  • Function: Recognize extracellular or endosomal pathogens. Signal mainly via MyD88 to activate NF-κB.
  • Key Examples:
    • TLR4: On cell surface; recognizes LPS from Gram-negative bacteria.
    • TLR2: On cell surface; recognizes peptidoglycan/lipoteichoic acid from Gram-positive bacteria.
    • TLR3, 7, 8: In endosomes; recognize viral nucleic acids (dsRNA, ssRNA).

• NOD-Like Receptors (NLRs)

  • Function: Cytosolic sensors of intracellular pathogens and cell damage.
  • Key Examples:
    • NOD2: Recognizes bacterial peptidoglycan. Mutations are strongly associated with Crohn’s disease.
    • NLRP3 Inflammasome: A cytosolic complex activated by diverse DAMPs (e.g., uric acid crystals). Its activation leads to caspase-1 activation, which cleaves pro-IL-1β into active IL-1β. This pathway is central to the inflammation seen in gout.

• RIG-I-Like Receptors (RLRs)

  • Function: Cytosolic sensors specializing in viral RNA. Their activation is crucial for producing Type I Interferons (IFN-α/β).
  • Key Example:
    • RIG-I: Recognizes specific RNA structures common in viral genomes (e.g., 5’-triphosphate RNA).

• High-Yield Associations

  • TLR4 Deficiency: Increased susceptibility to Gram-negative sepsis.
  • NOD2 Mutation: Increased risk for Crohn’s disease, particularly ileal disease.
  • NLRP3/Inflammasome: Gout (activated by uric acid crystals), autoinflammatory syndromes.