Pattern Recognition Receptors


Multicellular organisms continually come into contact with microbes in the environment, and protecting themselves from infection is vital to their survival. The innate immune system has a critically important role in acting as a first line of defence against this threat, by rapidly detecting and destroying any foreign invaders. Recognition of pathogens by the innate immune system is achieved through the actions of a large collection of pattern recognition receptors that bind to unique features of pathogens called pathogen‐associated molecular patterns that are not normally found in the host. Recognition is followed by the production of cytokines and chemokines and activation of innate immune responses that restrict, destroy and dispose of the pathogen and promote the subsequent activation of an adaptive immune response.

Key Concepts

  • Pattern recognition receptors (PRRs) detect foreign molecules associated with pathogens, termed pathogen‐associated molecular patterns (PAMPs).
  • PAMPs are specific to groups of pathogens and are not normally found in the host.
  • PRRs are found in different tissues and in different subcellular compartments according to the types of pathogen that they recognise.
  • Activation of PRRs leads to innate immune responses that destroy the pathogen.

Keywords: innate immunity; pattern recognition receptor; pathogen‐associated molecular pattern; cytokines; inflammasome

Figure 1. Toll‐like receptors (TLRs). TLRs exist as homo‐ or hetero‐dimeric transmembrane proteins located on the plasma membrane (PM) or on the endosome. The leucine‐rich repeat (LRR) domain faces the extracellular space or lumen of the endosome and is responsible for ligand binding. The cytoplasmic tail contains the Toll/interleukin‐1 receptor (TIR) domain that interacts with adaptor proteins that mediate signal transduction.
Figure 2. Intracellular nucleic acid receptors. The RLRs contain a DExD/H box RNA helicase domain responsible for binding dsRNA ligands and two N‐terminal caspase activation and recruitment domains (CARDs) that interact with the adaptor protein MAVS to activate downstream signalling. The DNA sensor cyclic GMP‐AMP (GAMP) synthase (cGAS) generates cGAMP from ATP and GTP, which activates stimulator of interferon genes (STING). Foreign DNA in the nucleus is detected by the pyhin protein IFI16 that has two HIN domains that bind DNA and a single N‐terminal pyrin domain (PYD). Activated IFI16 translocates into the cytoplasm to activate both STING and the inflammasome. AIM2 contains a C‐terminal HIN domain and an N‐terminal PYD that interacts with ASC to form the inflammasome.
Figure 3. Nucleotide‐binding leucine‐rich repeat containing receptors (NLRs). The NLRs contain a central nucleotide‐binding and oligomerisation domain (NOD) and C‐terminal leucine‐rich repeats (LRRs) that are responsible for ligand binding. The NLRs are grouped into subfamilies based on the composition of their N‐terminal domains. NAIP contains three baculovirus inhibitor of apoptosis protein repeat (BIR) domains. The NLRC subfamily contains one or two CARDs, and the NLRP subfamily has a pyrin domain (PYD) at the N‐terminus. These N‐terminal domains transmit signals to downstream adaptors.
Figure 4. C‐type lectin receptors and scavenger receptors. The C‐type lectin receptors are single‐pass transmembrane proteins characterised by the presence of one or more extracellular C‐type lectin‐like domains (CTLDs) that bind various carbohydrate and non‐carbohydrate ligands. Dectin‐1 has an immunoreceptor tyrosine‐based activation motif (ITAM) on its cytoplasmic tail that interacts with Syk, whereas Dectin‐2 and Mincle lack their own ITAM motif and instead interact with the ITAM‐containing FcRγ. DC‐SIGN has a single CTLD and exists as a tetramer, whereas the mannose receptor has a more extensive extracellular domain containing eight CTLDs. The scavenger receptors SR‐A1 and SR‐A6 (MARCO) exist as homotrimers with a single transmembrane domain, an α‐helical coiled‐coil domain (α) (SR‐A1 only), a collagenous domain (CD) and a cysteine‐rich domain (C). SR‐B2 has two transmembrane domains with an extracellular ligand‐binding loop and intracellular N‐ and C‐terminal tails.


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Further Reading

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Yoneyama M, Onomoto K, Jogi M, et al. (2015) Viral RNA detection by RIG‐I‐like receptors. Current Opinion in Immunology 32: 48–53.

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Childs, KS, and Goodbourn, S(May 2017) Pattern Recognition Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020175.pub2]