Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties.
Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern recognition molecules of innate immunity that are conserved from insects to humans. Various PGRPs are reported to have diverse functions: they bind bacterial molecules, digest PGN, and are essential to the Toll pathway in Drosophila. One family member, bovine PGN recognition protein-S (bPGRP-S), has been found to bind and kill microorganisms in a PGN-independent manner, raising questions about the identity of the bPGRP-S ligand. Addressing this, we have determined the binding and microbicidal properties of bPGRP-S in a range of solutions approximating physiologic conditions. In this study we show that bPGRP-S interacts with other bacterial components, including LPS and lipoteichoic acid, with higher affinities than for PCP, as determined by their abilities to inhibit bPGRP-S-mediated killing of bacteria. Where and how PGRPs act in vivo is not yet clear. Using Immunogold electron microscopy, PGRP-S was localized to the dense/large granules of naive neutrophils, which contain the oxygen-independent bactericidal proteins of these cells, and to the neutrophil phagolysosome. In addition, Immunogold staining and secretion studies demonstrate that neutrophils secrete PGRP-S when exposed to bacteria. Bovine PGRP-S can mediate direct lysis of heat-killed bacteria; however, PGRP-S-mediated killing of bacteria is independent of this activity. Evidence that bPGRP-S has multiple activities and affinity to several bacterial molecules challenges the assumption that the PGRP family of proteins recapitulates the evolution of TLRs. Mammalian PGRPs do not have a single antimicrobial activity against a narrow range of target organisms; rather, they are generalists in their affinity and activity.
Tydell
C Chace
CC
Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA. chacetyd@caltech.edu
Yuan
Jun
J
Tran
Patti
P
Selsted
Michael E
ME
D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000378:metabolism; D008089:Listeria monocytogenes / Q000187:drug effects; D016253:Microscopy, Immunoelectron; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein