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Article Dans Une Revue Nature Microbiology Année : 2018

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

Résumé

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.

Dates et versions

hal-01911327 , version 1 (02-11-2018)

Identifiants

Citer

Angelino T. Tromp, Michiel van Gent, Pauline Abrial, Amandine Martin, Joris P. Jansen, et al.. Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin. Nature Microbiology, 2018, 3 (6), pp.708-717. ⟨10.1038/s41564-018-0159-x⟩. ⟨hal-01911327⟩
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