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Cell Microbiol. 2013 Oct;15(10):1753-65. doi: 10.1111/cmi.12147. Epub 2013 May 3.

Pneumococcal immune evasion: ZmpC inhibits neutrophil influx.

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  • 1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Abstract

Neutrophil recruitment is essential in clearing pneumococcal infections. The first step in neutrophil extravasation involves the interaction between P-selectin on activated endothelium and P-Selectin Glycoprotein 1 (PSGL-1) on neutrophils. Here, we identify pneumococcal Zinc metalloproteinase C as a potent inhibitor of PSGL-1. ZmpC degrades the N-terminal domain of PSGL-1, thereby disrupting the initial rolling of neutrophils on activated human umbilical vein endothelial cells. Furthermore, mice infected with wild-type strain in the model of pneumococcal pneumonia showed lower lungs neutrophil infiltration compare to animals infected with ZmpC mutant. In addition, we confirmed the association of zmpC with serotype 8 and 11A and found it to be associated with serotype 33F as well. In conclusion, wereport PSGL-1 as a novel target for ZmpC and show that ZmpC inhibits neutrophil extravasation during pneumococcal pneumonia.

PMID:
23601501
DOI:
10.1111/cmi.12147
[PubMed - indexed for MEDLINE]
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