title: Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity.
abstract: Innate immune responses to bacteria require cooperative interactions between host recognition molecules and phagocytes. The peptidoglycan recognition proteins (PGRPs) are a large group of proteins found in insects and mammals that bind to bacterial peptidoglycan (PGN). PGRP-S is located with other antimicrobial proteins, such as lysozyme, in the granules of human neutrophils. Whereas both PGRP-S and lysozyme recognize PGN, the exact binding specificity of human PGRP-S, its functional activity, and its potential synergy with other neutrophil-derived bactericidal proteins such as lysozyme have not been determined. Here we show that human PGRP-S binds to and inhibits the growth of Staphylococcus aureus (containing lysine-type PGN) and Escherichia coli (containing mesodiaminopimelic acid-type PGN). The binding affinity and thus antimicrobial activity of PGRP-S is determined by the third amino acid in the PGN stem peptide. Furthermore, the antimicrobial effect of PGRP-S against E coli is synergistic with lysozyme, and lysozyme and PGRP-S colocalize in neutrophil extracellular traps (NETs), suggesting that these granule-derived proteins act together to kill bacteria trapped in the NETs. Taken together, these results indicate that human PGRP-S plays a role in innate immunity in the context of neutrophils by contributing to the killing of intracellular and extracellular bacteria.
authors.affiliation: Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Cho
authors.forename: Iain P
authors.initials: IP
authors.lastname: Fraser
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
authors.forename: R Alan B
authors.initials: RA
authors.lastname: Ezekowitz
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D019921:Biotinylation; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D008856:Microscopy, Fluorescence; D009113:Muramidase / Q000737:chemistry; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology*; D010457:Peptidoglycan / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D002352:Carrier Proteins; D010457:Peptidoglycan; D011994:Recombinant Proteins; C118897:peptidoglycan recognition protein; D009113:Muramidase