Host responses and defense against invading micro-organisms depend on highly conserved innate immune recognition systems that react with conserved motifs found uniquely in microbes. The Toll-like receptors are related proteins mediating inflammatory responses in a wide variety of cells, each receptor triggered by a distinct subset of microbial products. Host peptidoglycan recognition proteins (PGRPs), by contrast, share the ability to bind bacterial cell wall peptidoglycan (fragments) but are expressed at different cellular and tissue sites, suggesting that each PGRP may link peptidoglycan recognition to distinct host responses (Werner et al, Proc Nat Acad Sci U S A. 2000;97:13772-13777; Liu et al, J Biol Chem. 2001;276:34686-34694). Genes encoding 4 different PGRPs have been identified in the human genome by homology to conserved insect PGRP domains (Liu et al). One, PGRP-S, is highly expressed in bone marrow and encodes an approximately 19-kDa protein present in neutrophils, cells that play an essential early role in host defense against many invading bacteria (Liu et al; Liu et al, J Biol Chem. 2000;275:24490-24499).
To test the possible role of PGRP-S in host defense against bacterial infections, Dziarski and colleagues (page 689) have produced PGRP-S–deficient mice and, in so doing, demonstrate a role for PGRP-S in in vitro bacterial killing by neutrophils and in vivo clearance of intraperitoneal bacterial infection. The localization of PGRP-S in readily mobilized granules suggests not only a role in intracellular cytotoxicity after phagocytosis, as is shown, but also possible extracellular roles within neutrophil-rich inflammatory exudates. These studies reveal novel effector functions of mammalian PGRP-S and suggest that although while peptidoglycan recognition has been conserved within insect and mammalian orthologues, effector functions have changed to coordinate PGRP function with evolving organizations of host defense against bacteria.