Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity

Hyun Cho Ju, Iain P. Fraser, Koichi Fukase, Shoichi Kusumoto, Yukari Fujimoto, Gregory L. Stahl, R. Alan B. Ezekowitz

Research output: Contribution to journalArticle

94 Citations (Scopus)

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 neutrophilderived 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.

Original languageEnglish
Pages (from-to)2551-2558
Number of pages8
JournalBlood
Volume106
Issue number7
DOIs
Publication statusPublished - 2005 Oct

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Ju, H. C., Fraser, I. P., Fukase, K., Kusumoto, S., Fujimoto, Y., Stahl, G. L., & Ezekowitz, R. A. B. (2005). Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity. Blood, 106(7), 2551-2558. https://doi.org/10.1182/blood-2005-02-0530