Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)–deficient mice

• Published in: Blood Vol. 102; no. 2; pp. 689 - 697
• Main Authors: Dziarski, Roman, Platt, Kenneth A., Gelius, Eva, Steiner, Håkan, Gupta, Dipika
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.07.2003; The Americain Society of Hematology
• Subjects: Animals; Bacteremia - etiology; Bacteremia - immunology; Bacteremia - microbiology; Bacteremia/etiology/immunology/microbiology; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - physiology; Carrier Proteins/genetics/physiology; Chimera; Cytoplasmic Granules - metabolism; Evolution, Molecular; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Predisposition to Disease; Gram-Negative Bacterial Infections - etiology; Gram-Negative Bacterial Infections - immunology; Gram-Negative Bacterial Infections/etiology/immunology; Gram-Positive Bacterial Infections - etiology; Gram-Positive Bacterial Infections - immunology; Gram-Positive Bacterial Infections/etiology/immunology; Immunobiology; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-6/biosynthesis/genetics; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Molecular Sequence Data; Myeloid cells: ontogeny, maturation, markers, receptors; Neutrophils - pathology; Peritonitis - etiology; Peritonitis - immunology; Peritonitis - microbiology; Peritonitis/etiology/immunology/microbiology; Phagocytosis - physiology; Polynuclears; Species Specificity; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha/biosynthesis/genetics; Infection; Peptidoglycan; Vertebrata; Mammalia; Mouse; Gram positive bacteria; Animal; Rodentia; Granulocyte; Natural immunity; Neutrophil; Bactericidal effect; Inbred ICR; Evolution; Mice; Molecular; Inbred C57BL; Knockout
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-12-3853

Insect peptidoglycan recognition protein-S (PGRP-S), a member of a family of innate immunity pattern recognition molecules conserved from insects to mammals, recognizes bacterial cell wall peptidoglycan and activates 2 antimicrobial defense systems, prophenoloxidase cascade and antimicrobial peptides through Toll receptor. We show that mouse PGRP-S is present in neutrophil tertiary granules and that PGRP-S–deficient (PGRP-S-/-) mice have increased susceptibility to intraperitoneal infection with gram-positive bacteria of low pathogenicity but not with more pathogenic gram-positive or gram-negative bacteria. PGRP-S-/- mice have normal inflammatory responses and production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Neutrophils from PGRP-S-/- mice have normal phagocytic uptake of bacteria but are defective in intracellular killing and digestion of relatively nonpathogenic gram-positive bacteria. Therefore, mammalian PGRP-S functions in intracellular killing of bacteria. Thus, only bacterial recognition by PGRP-S, but not its effector function, is conserved from insects to mammals.