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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-12-3853.

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Submitted December 19, 2002
Accepted March 11, 2003

Defect in neutrophil killing and increased susceptibility to infection with non-pathogenic Gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice

Roman Dziarski*, Kenneth A Platt, Eva Gelius, Hakan Steiner, and Dipika Gupta

Northwest Center for Medical Education, Indiana University School of Medicine, Gary, IN, USA
Lexicon Genetics, Woodlands, TX, USA
Department of Microbiology, Stockholm University, Stockholm, Sweden

* Corresponding author; email: rdziar{at}iun.edu.

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 two 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 TNF-{alpha} and IL-6. Neutrophils from PGRP-S-/- mice have normal phagocytic uptake of bacteria, but are defective in intracellular killing and digestion of relatively non-pathogenic 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.


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