TY - JOUR
T1 - Pneumococcal immune evasion: ZmpC inhibits neutrophil influx
AU - Surewaard, Bas G. J.
AU - Trzciński, Krzysztof
AU - Jacobino, Shamir R.
AU - Hansen, Ivo S.
AU - Vughs, Mignon M.
AU - Sanders, Elisabeth A. M.
AU - van der Ende, Arie
AU - van Strijp, Jos A. G.
AU - de Haas, Carla J. C.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
U2 - https://doi.org/10.1111/cmi.12147
DO - https://doi.org/10.1111/cmi.12147
M3 - Article
C2 - 23601501
SN - 1462-5814
VL - 15
SP - 1753
EP - 1765
JO - Cellular microbiology
JF - Cellular microbiology
IS - 10
ER -