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dc.contributor.authorTromp, Angelino T
dc.contributor.authorVan Gent, Michiel
dc.contributor.authorAbrial, Pauline
dc.contributor.authorMartin, Amandine
dc.contributor.authorJansen, Joris P
dc.contributor.authorDe Haas, Carla JC
dc.contributor.authorVan Kessel, Kok PM
dc.contributor.authorBardoel, Bart W
dc.contributor.authorKruse, Elisabeth
dc.contributor.authorBourdonnay, Emilie
dc.contributor.authorBoettcher, Michael
dc.contributor.authorMcManus, Michael T
dc.contributor.authorDay, Christopher J
dc.contributor.authorJennings, Michael P
dc.contributor.authorLina, Gerard
dc.contributor.authorVandenesch, Francois
dc.contributor.authorVan Strijp, Jos AG
dc.contributor.authorLebbink, Robert Jan
dc.contributor.authorHaas, Pieter-Jan A
dc.contributor.authorHenry, Thomas
dc.contributor.authorSpaan, Andras N
dc.description.abstractThe 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.
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofjournalNature Microbiology
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchMedical Microbiology
dc.titleHuman CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorJennings, Michael P.
gro.griffith.authorDay, Christopher J.

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