The innate immune response, providing defense against infection, relies on the ability of immune cells to detect the presence of pathogens. This is achieved through a range of pattern recognition receptor proteins including the Toll-like receptors, the nucleotide oligomerization domain-like (NOD-like) receptors, the retinoic acid inducible gene-like (RIG-like) receptors, and a number of DNA-sensing molecules. The latter are the subject of this section of the website.

Absent in melanoma (AIM)-like receptors (ALRs)

ALR family proteins act as cytosolic DNA sensors in host defence against invading pathogens [2,5], and are also implicated in autoimmune diseases involving self DNA. The four genes encoding human proteins belonging to this family form a cluster on chromosome 1. The ALR gene family has little preserved orthology among mammals [1], complicating interpretation of experimental results between the different model systems used to investigate ALR function. Mice have 13 genes encoding ALR proteins, with only human AIM2 and mouse Aim2 showing 1-1 orthology.
Structurally ALR proteins possess an N-terminal pyrin domain which facilitates recruitment of signaling adaptors (critical for the assembly of inflammasomes), and one or two copies of the oligonucleotide binding HIN-200 domain at the C-terminus, which are involved in ligand recognition through electroststic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone [3-4]- see figure below.

Mutations in ALRs have been linked to the development of auto-inflammatory and autoimmune diseases.

C-type lectin-like receptors (CLRs)

CLRs are a large family of receptors with a diverse range of functions. Several family members recognize ligands on pathogens including fungi, viruses, bacteria, and helminths, some have endocytic activity targeting their ligands to intracellular vesicles for antigen processing and presentation, and they can be membrane anchored or soluble. Most, but not all, CLRs are Ca²⁺-dependent and contain a carbohydrate-binding domain. We include some of the best characterized CLRs in this section of the website, including those considered potential drug and vaccine development targets.

Catalytic receptor PRRs included in the Guide To PHARMACOLOGY are:
Toll-like receptors (TLRs)
Nucleotide-binding oligomerization domain-like receptors (NLRs, also known as NOD-like receptors), and
RIG-I-like receptors (RLRs)

1. Brunette RL, Young JM, Whitley DG, Brodsky IE, Malik HS, Stetson DB. (2012) Extensive evolutionary and functional diversity among mammalian AIM2-like receptors. J Exp Med, 209 (11): 1969-83. [PMID:23045604]

2. Bryant CE, Orr S, Ferguson B, Symmons MF, Boyle JP, Monie TP. (2015) International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease. Pharmacol Rev, 67 (2): 462-504. [PMID:25829385]

3. Jin T, Perry A, Jiang J, Smith P, Curry JA, Unterholzner L, Jiang Z, Horvath G, Rathinam VA, Johnstone RW et al.. (2012) Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity, 36 (4): 561-71. [PMID:22483801]

4. Li H, Wang ZX, Wu JW. (2014) Purification, characterization and docking studies of the HIN domain of human myeloid nuclear differentiation antigen (MNDA). Biotechnol Lett, 36 (5): 899-905. [PMID:24557068]

5. Ratsimandresy RA, Dorfleutner A, Stehlik C. (2013) An Update on PYRIN Domain-Containing Pattern Recognition Receptors: From Immunity to Pathology. Front Immunol, 4: 440. [PMID:24367371]