Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice.
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 alpha (TNF-alpha) 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.
Dziarski
Roman
R
Northwest Center for Medical Education, Indiana University School of Medicine, 3400 Broadway, Gary, IN 46408, USA. rdziar@iun.edu
Platt
Kenneth A
KA
Gelius
Eva
E
Steiner
Håkan
H
Gupta
Dipika
D
D000818:Animals; D016470:Bacteremia / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002678:Chimera; D003594:Cytoplasmic Granules / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D020022:Genetic Predisposition to Disease; D016905:Gram-Negative Bacterial Infections / Q000209:etiology* / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000209:etiology* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000473:pathology*; D010538:Peritonitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000502:physiology*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D002352:Carrier Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C118897:peptidoglycan recognition protein