Pattern recognition receptors, or PRRs, are a class of proteins which are employed by the cells of the immune system to identify molecules common to microbial pathogens but not present in mammalian cells. They are key elements in innate immunity as well as influence the development of adaptative immunity. Among the molecules recognised by these PRRs are: lipopolysaccharide (LPS) of gram negative bacteria, peptidoglycans and lipotechoic acids from Gram positive bacteria, mannose residues, bacterial DNA, N-formylmethionine, viral double-stranded RNA and fungal glucans. The specific molecular sequences identified by a given PRR are its PAMPs: pathogen-associated molecular patterns. Activation of PRRs trigger a series of biological responses including cytokine secretion.
PRRs are classified according to the patterns that they recognise, their functionality or their localization. According to functionality, PRRs are divided into endocytic PRRs and signaling PRRs. Endocytic PRRs promote the attachment, engulfment and destruction of microorganisms by phagocytes. These PRRs recognize carbohydrates and include mannose receptors of macrophages, glucan receptors present in all types of phagocytes and scavenger receptors that recognize charged ligands, are found on all phagocytes and mediate removal of apoptotic cells.
Pattern recognition receptors
Signaling PRRs comprise toll-like receptors (TLRs) and proteins also known as NOD proteins. Toll-like receptors were discovered in Drosophila and are known to trigger a series of mechanisms leading to the synthesis and secretion of several molecules including cytokines that are crucial to the development of innate or adaptative immune responses.
Toll-like receptors can be found as membrane receptors or inside the cell. At present, 11 TLRs have been found in all species. These receptors have been assigned numbers 1 to 11 (TLR1-TLR11). Other TLRs have been described in human and mice. Activation of TLRs induce pathways involving NFκB, MAP kinase and the secretion of pro-inflammatory cytokines as well as affect the expression of the so-called co-stimulatory molecules.
NOD proteins recognize intracellular peptidoglycan-derived MAMPs and transduce signals in the pathway of NFκB and MAP kinase. NOD proteins are so named as they contain a nucleotide-binding oligomerization domain which binds nucleotide triphosphate. NODs signal via N-terminal CARD domains to activate downstream gene induction events.
These may be considered a second category of NOD-like cytoplasmic proteins that may have a variety of functions. Current understanding suggests some of these proteins recognize endogenous or microbial molecules or stress responses and form oligomers with caspase-1 to cleave IL-1 into its active form.
A third type of PRRs are the secreted PRRs. Complement receptors, collectins, pentraxin proteins such as serum amyloid and C-reactive protein, lipid transferases and peptidoglycan recognition proteins (PGRs) are included in this group.
Intracellular recognition of viral double-stranded RNA has been shown to be mediated by a group of RNA Helicases which in turn recruit factors to activate antiviral gene programs.