The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors

Nat Commun. 2014 Nov 11;5:5438. doi: 10.1038/ncomms6438.

Abstract

Evasion of the host phagocyte response by Staphylococcus aureus is crucial to successful infection with the pathogen. γ-haemolysin AB and CB (HlgAB, HlgCB) are bicomponent pore-forming toxins present in almost all human S. aureus isolates. Cellular tropism and contribution of the toxins to S. aureus pathophysiology are poorly understood. Here we identify the chemokine receptors CXCR1, CXCR2 and CCR2 as targets for HlgAB, and the complement receptors C5aR and C5L2 as targets for HlgCB. The receptor expression patterns allow the toxins to efficiently and differentially target phagocytic cells. Murine neutrophils are resistant to HlgAB and HlgCB. CCR2 is the sole murine receptor orthologue compatible with γ-haemolysin. In a murine peritonitis model, HlgAB contributes to S. aureus bacteremia in a CCR2-dependent manner. HlgAB-mediated targeting of CCR2(+) cells highlights the involvement of inflammatory macrophages during S. aureus infection. Functional quantification identifies HlgAB and HlgCB as major secreted staphylococcal leukocidins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / physiology*
  • Bacterial Toxins*
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Hemolysin Proteins / physiology*
  • Humans
  • Macrophages / microbiology
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peritonitis / microbiology
  • Peritonitis / pathology
  • Peritonitis / physiopathology
  • Phagocytes / microbiology*
  • Phagocytes / pathology
  • Receptors, CCR2 / deficiency
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / physiology*
  • Receptors, Chemokine / physiology*
  • Receptors, Complement / physiology
  • Receptors, Interleukin-8A / physiology
  • Receptors, Interleukin-8B / physiology
  • Staphylococcal Infections / pathology
  • Staphylococcal Infections / physiopathology*
  • Staphylococcus aureus*

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Hemolysin Proteins
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Complement
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • gamma-hemolysin, Staphylococcus aureus