Human Peptidoglycan Recognition Protein 1 in Innate Immunity

AbstractInnate 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 neutrophil-derived 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. (Blood. 2005;106:2551-2558)

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Mouse Peptidoglycan Recognition Protein PGLYRP-1 Plays a Role in the Host Innate Immune Response againstListeria monocytogenesInfection

Infection and Immunity ◽

10.1128/iai.00466-10 ◽

2010 ◽

Vol 79 (2) ◽

pp. 858-866 ◽

Cited By ~ 23

Author(s):

Arihiro Osanai ◽

Hiroshi Sashinami ◽

Krisana Asano ◽

Sheng-Jun Li ◽

Dong-Liang Hu ◽

...

Keyword(s):

Innate Immunity ◽

Antibacterial Activities ◽

Bacterial Number ◽

Necrosis Factor Alpha ◽

Peptidoglycan Recognition Protein ◽

Recombinant Mouse ◽

Tnf Α ◽

Recognition Protein ◽

Ifn Γ ◽

Hepatocyte Cells

ABSTRACTThe role of mouse peptidoglycan recognition protein PGLYRP-1 in innate immunity againstListeria monocytogenesinfection was studied. The recombinant mouse PGLYRP-1 and a polyclonal antibody specific to PGLYRP-1 were prepared. The mouse PGLYRP-1 showed antibacterial activities againstL. monocytogenesand other Gram-positive bacteria. PGLYRP-1 mRNA expression was induced in the spleens and livers of mice infected withL. monocytogenes. The viable bacterial number increased, and the production of cytokines such as gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) was reduced in mice when mice had been injected with anti-PGLYRP-1 antibody before infection. The levels of IFN-γ and TNF-α titers in the organs were higher and the viable bacterial number was reduced in mice injected with recombinant mouse PGLYRP-1 (rmPGLYRP-1) before infection. PGLYRP-1 could directly induce these cytokines in spleen cell cultures. The elimination of intracellular bacteria was upregulated in NMuLi hepatocyte cells overexpressing PGLYRP-1. The enhancement of the elimination ofL. monocytogenesfrom the organs was observed in IFN-γ−/−mice by rmPGLYRP-1 administration but not in TNF-α−/−mice. These results suggest that PGLYRP-1 plays a role in innate immunity againstL. monocytogenesinfection by inducing TNF-α.

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