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The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors.
- Source :
-
Nature communications [Nat Commun] 2014 Nov 11; Vol. 5, pp. 5438. Date of Electronic Publication: 2014 Nov 11. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Cells, Cultured
Disease Models, Animal
Female
Humans
Macrophages microbiology
Macrophages pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Peritonitis microbiology
Peritonitis pathology
Peritonitis physiopathology
Phagocytes pathology
Receptors, CCR2 deficiency
Receptors, CCR2 genetics
Receptors, Complement physiology
Receptors, Interleukin-8A physiology
Receptors, Interleukin-8B physiology
Staphylococcal Infections pathology
Bacterial Proteins physiology
Bacterial Toxins
Hemolysin Proteins physiology
Phagocytes microbiology
Receptors, CCR2 physiology
Receptors, Chemokine physiology
Staphylococcal Infections physiopathology
Staphylococcus aureus
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 25384670
- Full Text :
- https://doi.org/10.1038/ncomms6438