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

András N. Spaan, Manouk Vrieling, Pierre Wallet, Cédric Badiou, Tamara Reyes-Robles, Elizabeth A. Ohneck, Yvonne Benito, Carla J. C. de Haas, Christopher J. Day, Michael P. Jennings, Gérard Lina, François Vandenesch, Kok P. M. van Kessel, Victor J. Torres, Jos A. G. van Strijp () and Thomas Henry
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András N. Spaan: University Medical Center Utrecht
Manouk Vrieling: University Medical Center Utrecht
Pierre Wallet: CIRI, International Center for Infectiology Research, Université Lyon 1 and Ecole Normale Supérieure de Lyon
Cédric Badiou: CIRI, International Center for Infectiology Research, Université Lyon 1 and Ecole Normale Supérieure de Lyon
Tamara Reyes-Robles: New York University School of Medicine
Elizabeth A. Ohneck: New York University School of Medicine
Yvonne Benito: CIRI, International Center for Infectiology Research, Université Lyon 1 and Ecole Normale Supérieure de Lyon
Carla J. C. de Haas: University Medical Center Utrecht
Christopher J. Day: Institute for Glycomics, Griffith University
Michael P. Jennings: Institute for Glycomics, Griffith University
Gérard Lina: CIRI, International Center for Infectiology Research, Université Lyon 1 and Ecole Normale Supérieure de Lyon
François Vandenesch: CIRI, International Center for Infectiology Research, Université Lyon 1 and Ecole Normale Supérieure de Lyon
Kok P. M. van Kessel: University Medical Center Utrecht
Victor J. Torres: New York University School of Medicine
Jos A. G. van Strijp: University Medical Center Utrecht
Thomas Henry: CIRI, International Center for Infectiology Research, Université Lyon 1 and Ecole Normale Supérieure de Lyon

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6438

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