A peptidoglycan recognition protein in innate immunity conserved from insects to humans

Abstract

Innate nonself recognition must rely on common structures of invading microbes. In a differential display screen for up-regulated immune genes in the moth Trichoplusia ni we have found mechanisms for recognition of bacterial cell wall fragments. One bacteria-induced gene encodes a protein that, after expression in the baculovirus system, was shown to be a peptidoglycan recognition protein (PGRP). It binds strongly to Gram-positive bacteria. We have also cloned the corresponding cDNA from mouse and human and shown this gene to be expressed in a variety of organs, notably organs of the immune system-i.e., bone marrow and spleen. In addition, purified recombinant murine PGRP was shown to possess peptidoglycan affinity. From our results and the sequence homology, we conclude that PGRP is a ubiquitous protein involved in innate immunity, conserved from insects to humans.

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“…The first member of this diverse family was cloned from mouse and designated as tag7. 69 Later, its insect homologue was cloned from insects and pathogen molecular pattern recognition was demonstrated, 70 thus leading to another name, PGRP, for peptidoglycan recognition protein.…”

“…71 It was designated tagL because it encodes the protein almost twice larger than Tag7/PGRP-S. Later, a large family of genes was identified in Drosophila and human genomes using the same approach. 72,73 Mammalian Tag7/PGRP-S has been cloned from mouse, 69 human, 70 rat, 74 and cow. 75 There are small extracellular proteins (19)(20)(21)(22)(23)(24), which structurally share homology with T phage lyzozyme but do not possess any amidaze activity.…”

“…75 There are small extracellular proteins (19)(20)(21)(22)(23)(24), which structurally share homology with T phage lyzozyme but do not possess any amidaze activity. Apart from their ability to recognize oligosaccharides and particularly peptidoglycan 70,75 cytotoxicity towards mammalian cells, 69,75,76 bactericidal and bacteriostatic activities 75 were detected. Tag7/PGRP-S is expressed in the spleen, brain, intestine, 69,74,77 bone marrow, 70 in lymphocytes 78 and neutrophils.…”

“…Apart from their ability to recognize oligosaccharides and particularly peptidoglycan 70,75 cytotoxicity towards mammalian cells, 69,75,76 bactericidal and bacteriostatic activities 75 were detected. Tag7/PGRP-S is expressed in the spleen, brain, intestine, 69,74,77 bone marrow, 70 in lymphocytes 78 and neutrophils. 70,75 Isoforms of mammalian TagL/PGRP-L are rather large proteins, which share strong C-terminal homology with Tag7/PGRP-S but also have transmembrane domain and intracellular N terminus.…”

“…Tag7/PGRP-S is expressed in the spleen, brain, intestine, 69,74,77 bone marrow, 70 in lymphocytes 78 and neutrophils. 70,75 Isoforms of mammalian TagL/PGRP-L are rather large proteins, which share strong C-terminal homology with Tag7/PGRP-S but also have transmembrane domain and intracellular N terminus. 71,73 TagL/ PGRP-L was found to be both secreted and membranebound proteins recognizing a wide variety of pathogens independently of the surface peptidoglycan.…”