B.G.J.S designed and performed research and wrote the article; K.T., S.R.J., I.S.H., M.M.V and A.v.d.E. performed the research; K.T., E.A.M.S., J.A.G.v.S., and C.J.C.d.H. participated in designing research; and all authors checked the final version of the manuscript. The authors declare no competing financial interests.
Pneumococcal immune evasion: ZmpC inhibits neutrophil influx
Article first published online: 3 MAY 2013
© 2013 John Wiley & Sons Ltd
Volume 15, Issue 10, pages 1753–1765, October 2013
How to Cite
Surewaard, B. G. J., Trzciński, K., Jacobino, S. R., Hansen, I. S., Vughs, M. M., Sanders, E. A. M., van der Ende, A., van Strijp, J. A. G. and de Haas, C. J. C. (2013), Pneumococcal immune evasion: ZmpC inhibits neutrophil influx. Cellular Microbiology, 15: 1753–1765. doi: 10.1111/cmi.12147
- Issue published online: 15 SEP 2013
- Article first published online: 3 MAY 2013
- Accepted manuscript online: 18 APR 2013 06:26AM EST
- Manuscript Accepted: 4 APR 2013
- Manuscript Revised: 21 MAR 2013
- Manuscript Received: 30 NOV 2012
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.