Key Points
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Peptidoglycan recognition proteins (PGRPs) are innate immunity molecules present in most invertebrate and vertebrate animals, but not in plants. Insects have up to 19 PGRPs, classified into short (S) and long (L) forms, and four mammalian PGRPs have been identified. All PGRPs have at least one C-terminal PGRP domain, which is homologous to bacteriophage and bacterial type 2 amidases.
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Insect short PGRPs are present in the haemolymph, cuticle, fat body cells and gut, whereas the long forms are mainly expressed in haemocytes and fat body cells. The expression of insect PGRPs is often upregulated by exposure to bacteria.
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Insect PGRPs are mainly inducers of proteolytic and signalling cascades. Each PGRP domain has one peptidoglycan-binding groove that is specific for muramyl-pentapeptide and that can discriminate between different types of bacterial peptidoglycan, containing either lysine or diaminopimelic acid. PGRPs generate downstream signals by ligand-induced dimerization or oligomerization.
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Short insect PGRPs (for example, PGRP-SA) are pattern recognition receptors that recognize lysine-containing peptidoglycan and trigger a proteolytic cascade that generates an activator of the Toll receptor.
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One long insect PGRP, PGRP-LC, is a transmembrane receptor that recognizes diaminopimelic acid-containing peptidoglycan and activates the IMD signal transduction pathway. Both the Toll and IMD pathways induce the production of antimicrobial peptides.
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Some insect and mammalian PGRPs are N-acetylmuramoyl-L-alanine amidases that hydrolyse bacterial peptidoglycan and reduce its pro-inflammatory activity.
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One mammalian PGLYRP, PGLYRP-2, has amidase activity. The three remaining mammalian PGRPs are bactericidal proteins that are secreted as disulphide-linked homo- and heterodimers. PGLYRP-1 is expressed primarily in PMN granules, and PGLYRP-3 and PGLYRP-4 are expressed in the skin, eyes, salivary glands, throat, tongue, esophagus, stomach and intestine. They kill bacteria by interacting with their cell-wall peptidoglycan, rather than permeabilizing their membranes, and synergize with antibacterial peptides.
Abstract
Peptidoglycan recognition proteins (PGRPs) are innate immunity molecules that are present in most invertebrate and vertebrate animals. All PGRPs function in antimicrobial defence and are homologous to the prokaryotic peptidoglycan-lytic type 2 amidases. However, only some PGRPs have the catalytic activity that protects the host from excessive inflammation, and most PGRPs have diversified to carry out other host-defence functions. Insect and mammalian PGRPs defend host cells against infection through very different mechanisms. Insect PGRPs activate signal transduction pathways in host cells or trigger proteolytic cascades in the haemolymph, both of which generate antimicrobial effectors. By contrast, mammalian PGRPs are directly bactericidal. Here, we review these contrasting modes of action.
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Acknowledgements
We thank members of the Royet laboratory for comments on the manuscript. Research in the authors' laboratories was supported by the National Institutes of Health (R.D.) and the Ministère de l'Education Nationale de la Recherche et de la Technologie, the Agence National pour la Recherche and the Fondation pour la Recherche Médicale (J.R.).
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Glossary
- Haemolymph
-
Circulatory fluid found in insects, which bathes the organs directly.
- Prophenoloxidase cascade
-
Serine-proteinase-based cascade leading to activation of a prophenoloxidase-activating proteinase, which converts inactive prophenoloxidase to active phenoloxidase and results in the generation of quinone and quinone intermediates. Polymerization of quinone intermediates can form melanin.
- Type 2 amidase
-
An enzyme that hydrolyses the lactyl-amide bond between the N-acetylmuramic acid and the first amino acid (L-alanine) of the stem peptide in bacterial peptidoglycan.
- Teichoic acid
-
A phosphate-rich, anionic polysaccharide that is attached to the peptidoglycan of Gram-positive bacteria. Most are polyglycerol phosphate or polyribitol phosphate and, in the case of lipoteichoic acids, have lipid modifications that allow association with the cytoplasmic membrane.
- Plasmatocyte
-
The main cell type found in insect haemolymph.
- Type IV secretion system
-
A syringe-like proteinaceous machinery that can transport bacterial protein or DNA effector molecules directly into a eukaryotic cell.
- Opsonin
-
A substance that binds to microorganisms and other cells and enhances their phagocytosis.
- RNA interference
-
(RNAi). The use of double-stranded RNAs with sequences that precisely match a given gene, to 'knock-down' the expression of that gene by directing RNA-degrading enzymes to destroy the encoded mRNA transcript.
- Polymorphonuclear leukocyte
-
(PMN). White blood cell with multilobed nuclei and cytoplasmic granules, which is involved in inflammatory responses.
- M cell
-
(Microfold cell). Cell type located in the Peyer's patches of the small intestine. Involved in antigen transport and interaction with bacterial pathogens.
- Peyer's patches
-
Specialized lymphoid follicles localized in the submucosa of the small intestine. They contain B-cell follicles and interfollicular T-cell areas, with an outer epithelial layer containing M cells.
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Royet, J., Dziarski, R. Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences. Nat Rev Microbiol 5, 264–277 (2007). https://doi.org/10.1038/nrmicro1620
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DOI: https://doi.org/10.1038/nrmicro1620
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