Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin

Nat Microbiol. 2018 Jun;3(6):708-717. doi: 10.1038/s41564-018-0159-x. Epub 2018 May 7.


The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / metabolism*
  • CRISPR-Cas Systems
  • Cell Line
  • Disease Models, Animal
  • Exotoxins / metabolism*
  • Hemolysin Proteins / metabolism
  • Humans
  • Leukocidins / metabolism*
  • Leukocyte Common Antigens / metabolism*
  • Mice
  • Mice, Knockout
  • Neutrophils / metabolism
  • Receptor, Anaphylatoxin C5a / genetics*
  • Staphylococcal Infections / genetics
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / pathogenicity*


  • Bacterial Proteins
  • Bacterial Toxins
  • C5AR1 protein, human
  • Exotoxins
  • Hemolysin Proteins
  • Leukocidins
  • Panton-Valentine leukocidin
  • Receptor, Anaphylatoxin C5a
  • gamma-hemolysin, Staphylococcus aureus
  • Leukocyte Common Antigens
  • PTPRC protein, human