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, Franҫois Vandenesch, Kok P.M. Van Kessel, Victor J. Torres, Jos A.G. Van Strijp*, Thomas Henry

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

78 Citations (Scopus)

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.

Original languageEnglish
Article number5438
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 11 Nov 2014
Externally publishedYes

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