Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity.
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.
Cho
Ju Hyun
JH
Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Fraser
Iain P
IP
Fukase
Koichi
K
Kusumoto
Shoichi
S
Fujimoto
Yukari
Y
Stahl
Gregory L
GL
Ezekowitz
R Alan B
RA
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
D000890:Anti-Infective Agents; D002352:Carrier Proteins; D010457:Peptidoglycan; D011994:Recombinant Proteins; C118897:peptidoglycan recognition protein; D009113:Muramidase