title: Pneumococcal immune evasion: ZmpC inhibits neutrophil influx.
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.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bas G J
authors.initials: BG
authors.lastname: Surewaard
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Trzciński
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Jacobino
authors.forename: Ivo S
authors.initials: IS
authors.lastname: Hansen
authors.forename: Mignon M
authors.initials: MM
authors.lastname: Vughs
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.forename: Carla J C
authors.initials: CJ
authors.lastname: de Haas
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D008168:Lung / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000473:pathology; D059748:Proteolysis; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D008666:Metalloendopeptidases; C478168:ZmpC protein, Streptococcus pneumoniae