Pneumococcal immune evasion: ZmpC inhibits neutrophil influx |
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| Authors: | Bas G J Surewaard Krzysztof Trzciński Shamir R Jacobino Ivo S Hansen Mignon M Vughs Elisabeth A M Sanders Arie van der Ende Jos A G van Strijp Carla J C de Haas |
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| Institution: | 1. Department of Medical Microbiology, University Medical Center Utrecht, , Utrecht, The Netherlands;2. Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, UMC Utrecht, , Utrecht, The Netherlands;3. Department of Medical Microbiology, Academic Medical Center, , Amsterdam, The Netherlands;4. Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, , Amsterdam, The Netherlands |
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| 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. |
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